A Phase 3 Randomized Study Comparing JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA, Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Subjects With Relapsed and Lenalidomide-Refractory Multiple Myeloma
Phase: PHASE3
Conditions: Multiple Myeloma
Sponsor: Janssen Research & Development, LLC

CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved, Date: 18 August 2022
Janssen Research & Development *
Clinical Protocol
A Phase 3 Randomized Study Comparing JNJ-68284528, a Chimeric Antigen Receptor T 
cell (CAR-T) Therapy Directed Against BCMA, versus Pomalidomide, Bortezomib and 
Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in 
Subjects with Relapsed and Lenalidomide-Refractory Multiple Myeloma
CARTITUDE-4
Protocol 68284528MMY3002; Phase 3   
AMENDMENT 4
JNJ-68284528 (ciltacabtagene autoleucel)
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development
studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen
Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Pharmaceutica NV; Janssen
Sciences Ireland UC; Janssen Biopharma Inc.; or Janssen Research & Development, LLC. The term
“sponsor” is used throughout the protocol to represent these various legal entities; the sponsor is
identified on the Contact Information page that accompanies the protocol.
United States sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
EudraCT NUMBER:    2019-001413-16
Status:
Approved  
Date:
18 August 2022
Prepared by:
Janssen Research & Development  
EDMS number:
EDMS-ERI-181176969, 5.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and 
may not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed 
by them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as 
privileged or confidential.
NCT04181827

JNJ-68284528 (ciltacabtagene autoleucel)
Clinical Protocol 68284528MMY3002 Amendment 4
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
2
Status: Approved,  Date: 18 August 2022
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
Amendment 4
18 August 2022
Amendment 3
14 June 2022
Amendment 2
02 July 2021
Amendment 1
20 March 2020
Original Protocol
25 October 2019
Amendment 4 (18 August 2022)
Overall Rationale for the Amendment: The reason for the amendment is to change the number of PFS 
events required to trigger the interim analysis. Per health authority request, the interim analysis will take 
place after approximately 75% of the total PFS events have been observed.
The changes made to the clinical protocol 68284528MMY3002 as part of Protocol Amendment 4 are listed 
below, including the rationale of each change and a list of all applicable sections. 
Section Number
and Name
Description of Change
Brief Rationale
1.1. Synopsis, 
Statistical Methods
Removed reference to the interim analysis PFS 
events used in the sample size calculation.
The number of PFS events required 
for the interim analysis was 
modified following health authority 
request 
4.1.2. Arm B;
9.5. Interim Analysis
The interim analysis for efficacy will occur at 
approximately 188 PFS events (change from 
approximately 165 events) which corresponds to 
75% of the total planned 250 PFS events 
(modification from 66% of the total planned PFS 
events) The estimated number of OS events at 
PFS IA will be changed accordingly.
1.3. Schedule of 
Activities (SoA), 
Table 1, Table 2, 
Table 3, Table 4,
Table 5
Revisions to clarify that subjects will be tested 
for IgG, IgA, IgM, IgD, and IgE at screening.
Only subjects identified as have IgD or IgE type 
myeloma at screening will need testing for IgD 
and IgE post screening.
Changes for clarity in collection 
and testing of samples for 
quantitative immunoglobulins.
1.3. Schedule of 
Activities (SoA), 
Table 3;Table 5
8.1.1. Myeloma 
Protein Measurements 
in Serum and Urine
Language added to provide clarity regarding 
when DSIFE testing is not needed for subjects in 
Arm A and Arm B.
Revisions for clarity
1.3. Schedule of 
Activities (SoA), 
Table 5;
8. Study Assessments 
and Procedures
8.9. Biomarkers
Added that sites will be notified if a subject has a 
sample that tests positive for RCL and that if a 
subject does not have a positive sample RCL will 
not be required to be collected after the 12-
month visit 
Addition for clarity
2.3. Benefit-Risk 
Assessment
The category of ‘other neurotoxicities’ was split 
into Movement and Neurocognitive Toxicity (ie, 
Parkinsonism), Cranial Nerve Palsies, Peripheral 
Neuropathy, and Guillain-Barré Syndrome.
Change to align with the current 
edition of the cilta-cel IB.
8. Study Assessments 
and Procedures
Added guidance regarding the types of 
procedures and documentation of procedures that 
To provide guidance for home 
health care and telehealth visits.

JNJ-68284528 (ciltacabtagene autoleucel)
Clinical Protocol 68284528MMY3002 Amendment 4
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Status: Approved,  Date: 18 August 2022
Section Number
and Name
Description of Change
Brief Rationale
can be conducted via home health care on an 
exceptional basis.
Amendment 3 (14 June 2022)
Overall Rationale for the Amendment:  The reason for the amendment is to inform investigators that 
patients receiving cilta-cel are possibly at a higher risk of severe/fatal outcomes from COVID-19 infection 
compared with patients who are receiving standard of care therapy, and to provide additional guidance for 
prevention and mitigation. Additional guidance for HLH and additional clarifications were also 
incorporated.
Section Number
and Name
Description of Change
Brief Rationale
2.3 Benefit-Risk Assessment; 
6.1.6.7 Serious Infections; 
6.5.1.3 Prophylaxis for 
Infections; 10.29 Appendix 29: 
Study Conduct During a 
Natural Disaster
Added guidance on measures to prevent and 
mitigate COVID-19 infection, including the 
importance of vaccines and other preventative 
measures, the use of prophylaxis therapy (eg, 
Evusheld, if available), and the use of antiviral 
therapy (eg, Paxlovid, if available) for
COVID-19 infection. 
To provide additional 
prevention and mitigation 
guidelines for COVID-19 
infections in patients treated 
with cilta-cel. 
8.3.1 Time Period and 
Frequency for Collecting 
Adverse Event and Serious 
Adverse Event Information; 
10.30 Appendix 30: Adverse 
Event Reporting Guidance for 
Study 68284528MMY3002
Added text to indicate that events of 
COVID-19 infection will be reported during 
the first-year post-infusion of cilta-cel.
To expand the reporting 
timeframe for COVID-19 
infections.
1.3 Schedule of Activities 
(SoA), Tables 4 and 5; 6.5 
Concomitant Therapy; 10.29 
Appendix 29: Study Conduct 
During a Natural Disaster
Specified that medications for the prevention 
and treatment of COVID-19, including 
vaccinations against COVID-19, will be 
reported until 1 year after cilta-cel infusion. 
To expand the reporting 
timeframe for COVID-19 
medications.
8.3.1 Time Period and 
Frequency for Collecting 
Adverse Event and Serious 
Adverse Event Information; 
10.30 Appendix 30: Adverse 
Event Reporting Guidance for 
Study 68284528MMY3002
For Arm B, added clarification of the 
requirement for expedited reporting (within 
24 hours) of any grade movement and 
neurocognitive toxicity (ie, parkinsonism).
To ensure this risk is 
communicated in an 
expedited fashion, consistent 
with health authority 
feedback. 
2.3 Benefit-Risk Assessment; 
6.1.6.1 Management of 
Cytokine Release Syndrome
Added language regarding features of HLH 
that may put subjects at high risk of bleeding 
and included additional measures to be taken 
if HLH is suspected. 
To increase awareness and 
provide additional guidance 
about the risk of HLH, 
consistent with health 
authority feedback.
8.3.1 Time Period and 
Frequency for Collecting 
Adverse Event and Serious 
Adverse Event Information;
Removed statement that “Grade 1 or 2 AEs of 
CRS and neurotoxicity would not qualify for 
expedited reporting unless they meet SAE 
criteria”
For clarity.
1.3 Schedule of Activities
(SoA), Table 5
The footnote for cytokine profiling (serum)
was changed from “l” to “n”.
Correction to fix error.
1.3 Schedule of Activities 
(SoA), Table 5
Added Study Days for each specific month
timepoint for MRD (bone marrow aspirate).
Revised for clarity.

JNJ-68284528 (ciltacabtagene autoleucel)
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Status: Approved,  Date: 18 August 2022
Section Number
and Name
Description of Change
Brief Rationale
1.3 Schedule of Activities 
(SoA), Table 5
Added language regarding collection of RCL 
samples.
Revised to include additional 
information for the RCL 
requirement.
1.3 Schedule of Activities 
(SoA), Table 5; 10.2 Appendix 
2: Clinical Laboratory Tests
Edits/footnotes added to clarify which 
subjects are required to do the CD4/CD8 
lymphocyte panel.
For Arm B in Table 5, the footnote ‘r’ was 
added for CD4/CD8 Lymphocyte panel.
Revised for clarity.
2.2.6.1 Pomalidomide, 
Bortezomib, and 
Dexamethasone; 
8.3.3 Pregnancy;
10.12 Appendix 12: 
Contraceptive and Barrier 
Guidance and Collection of 
Pregnancy Information
Reference to the Pomalyst was revised to add 
the generic name.
Revision to clarify that 
generic pomalidomide can be 
used.
6.1.5.3 Conditioning Regimen
Text added: If required, approval from the 
relevant health authorities for use of the 
product will be obtained in compliance with 
local regulations regarding notification and 
approval.
Revised for clarity and 
consistency with other 
studies in the program.
6.1.6.1 Management of 
Cytokine Release Syndrome
Table 11 (Guidelines for the Management of 
Cytokine Release Syndrome) reorganized and 
modified to include organ toxicity.
Revised based on health 
authority feedback.
6.1.6.2.1 CAR-T Cell-related 
Neurotoxicity (Immune 
Effector Cell-Associated 
Neurotoxicity Syndrome 
[ICANS])
Added guidance in text for treatment if 
concurrent CRS is suspected during a 
neurologic event.
Added for clarity.
6.1.6.2.1 CAR-T Cell-related 
Neurotoxicity (Immune 
Effector Cell-Associated 
Neurotoxicity Syndrome 
[ICANS])
Table 12 (Guidelines for the Management of 
Immune Effector Cell-Associated 
Neurotoxicity Syndrome [ICANS]) 
reorganized and modified based on ASTCT 
consensus criteria.
Revised based on health 
authority feedback.
6.6.2 Pomalidomide and 
Bortezomib Dose Modification 
for Hematologic Toxicity
Added that for Grade 1 neuropathy change in 
bortezomib frequency may be considered 
based on clinical judgement and/or 
institutional practice.
For Grade 1 with pain or Grade 2 added that a 
reduction of dosing by one level is a 
maximum dose of 1.0 mg/m2
Revisions for clarity.
6.6.2 Pomalidomide and 
Bortezomib Dose Modification 
for Hematologic Toxicity 
(Table 21, footnote d)
Clarified that change in the schedule of
bortezomib administration to once per week 
should occur on Days 1, 8, and 15.
Change made for clarity.
8 Study Assessments and 
Procedures
Updated the approximate blood volume to be 
collected from each subject.
Updated to address increase 
in volume for RCL and 
whole blood CyTOF
samples.
8.1.2 Imaging
Added language regarding the diagnostic 
quality if a CT scan is used.
The sentence was previously 
removed in error.
8.9 Biomarkers
Added language regarding post-infusion 
samples and included additional measures to 
be taken if RCL is negative or positive.
Revised for consistency with 
other studies in the program.

JNJ-68284528 (ciltacabtagene autoleucel)
Clinical Protocol 68284528MMY3002 Amendment 4
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Status: Approved,  Date: 18 August 2022
Section Number
and Name
Description of Change
Brief Rationale
10.2 Appendix 2: Clinical 
Laboratory Tests
Added a request to provide COVID-19 
antibody titers, if available, post cilta-cel 
infusion for up to 1 year.
Request for clarity regarding 
COVID-19 antibody 
reporting, including 
timeframe.
Amendment 2 (02 July 2021)
Overall Rationale for the Amendment:  Overall reasons for the amendment are to provide guidance on 
study conduct during the COVID-19 pandemic, to enable increased patient access via the lowering of 
inclusion criteria for study entry (ie, reduced serum monoclonal paraprotein levels), and to revise safety 
reporting requirements to allow extended data collection.
Revisions noted below are representative of the changes. In some cases, new text is displayed in bold font 
and deleted text noted with strikethrough.
Section Number
and Name
Description of Change
Brief Rationale
10.29 Appendix 29 Study 
Conduct During a Natural 
Disaster
Natural Disaster/COVID-19 appendix added.
Added to provide guidance 
on study conduct during the
COVID-19 pandemic, 
including considerations for 
vaccine administration.
5.2 Exclusion Criteria
Criterion 6 was updated to indicate that 
vaccination with live attenuated vaccines is 
not permitted 6 weeks prior to randomization.
Updated to maintain 
consistency with other 
sections and other studies in 
the program.
5.1 Inclusion Criteria
Criterion 2 was edited for the following
reasons:
!
To indicate a change in the serum 
monoclonal paraprotein (M-protein) level 
from ∀1.0 g/dL to ∀0.5 g/dL
!
To add a note that ‘If central and local 
laboratory studies are performed the 
same day, only the central laboratory 
results will be considered.’
Updated and clarified the 
criteria of measurable disease 
at screening necessary for a 
documented diagnosis of 
multiple myeloma (MM).
5.2 Exclusion Criteria
Criterion 18 was revised to remove ‘history of 
autoimmune disease within 2 years’
To increase patient access by 
providing a more inclusive 
patient population
10.7 Appendix 7: Criteria for 
Response to Multiple Myeloma 
Treatment
Footnote added to the table to indicate that 
patients with <0.5 g/dL at baseline cannot be 
assessed for minimal response.
Clarification and alignment 
with other sections of the 
protocol.
5.1 Inclusion Criteria
Criterion 6.1 was updated to Criterion 6.2 in 
order to clarify that subjects must be 
refractory to lenalidomide in at least one prior 
line.
Clarification.
4.1.2 Arm B
Updated section for the following:
!
To provide information on additional 
cycles of bridging therapy
!
To clarify that after PD, subjects will be 
followed for delayed adverse events 
(Arm A) and delayed adverse events 
including SPMs (Arm B)
!
To provide further monitoring details for 
subjects who progress in Arm B prior to 
receiving cilta-cel
Clarification and alignment 
with other sections of the 
protocol.

JNJ-68284528 (ciltacabtagene autoleucel)
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Status: Approved,  Date: 18 August 2022
Section Number
and Name
Description of Change
Brief Rationale
!
To provide the study number (ie, 
Study 68284528MMY4002) of the 
subsequent long-term follow-up study for 
the continued monitoring of subjects 
treated with cilta-cel.
7.1.2 Discontinuation of Study 
Treatment for Arm B
Updated section to clarify that after PD, 
subjects will be followed for delayed adverse 
events (Arm A) and delayed adverse events 
including SPMs (Arm B).
Clarification and alignment 
with other sections of the 
protocol.
1.1 Synopsis, Intervention 
Groups and Duration
Text clarified to note that:
‘After confirmed PD, subjects will be 
followed for survival, subsequent anti-
myeloma therapies, and delayed AEs 
including SPMs every 16 weeks until the end 
of the study.’
Clarification and alignment 
with other sections of the 
protocol.
1.3 Schedule of Activities
(SoA), Table 1
Text for bone marrow aspirate and core biopsy 
procedure was revised to note sampling 
conditions for rescreened patients.
Clarification
1.3 Schedule of Activities 
(SoA), Tables 1, 2, 3, and 4
Table 1: Deleted the assessment of ‘secondary 
primary malignancy’ from the screening phase 
as it is assessed from randomization onwards, 
not from the signing of the Informed Consent 
Form (ICF).
Tables 2, 3, and 4: Text for assessment of 
‘secondary primary malignancy’ was clarified 
to note that assessment is from the time of 
randomization, and not from signing of the 
ICF.
Correction
1.3 Schedule of Activities 
(SoA), Tables 2, 3, and 5
In order to indicate that collection of the 
EQ-5D-5L questionnaire in the post-treatment 
follow-up phase (ie, Post-PD) has been 
revised from every 6 months until EOS to 
every 16 weeks ±14 days, the footnote  (and 
corresponding in-table cross-reference) was 
deleted.
Revision of collection period.
1.2 Schema;
1.3 Schedule of Activities 
(SoA), Tables 2 and 3
Revised text to indicate that the end of 
treatment is to occur within 30 days of the last 
dose.
Clarified timing of the end of 
treatment.
1.2 Schema
Text revised to indicate that patients will be 
followed-up for survival status, serious adverse 
events, and delayed adverse events.
Updated assessments made 
during the follow-up period.

JNJ-68284528 (ciltacabtagene autoleucel)
Clinical Protocol 68284528MMY3002 Amendment 4
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Status: Approved,  Date: 18 August 2022
Section Number
and Name
Description of Change
Brief Rationale
1.3 Schedule of Activities 
(SoA), Tables 2, 3, 4, and 5
Revised timing of plasmacytoma assessment 
via radiology to:
Table 2: ‘C4D1C5D1 (±7 14 days) and then 
every 12 weeks (±7 14 days)’.
Table 3: ‘C3D1C4D1 (±7 14 days) and then 
every 12 weeks (±7 14 days)
In Table 4, a window of ≤72 hours was added 
for plasmacytoma assessment at Apheresis. 
Information was added regarding the timing of 
on plasmacytoma assessment during the 
Treatment Phase.
In Table 5, the window for plasmacytoma 
assessment via radiology was revised to 
±14 days.
Clarified information 
regarding plasmacytoma 
assessment, including 
updates to timing and 
extension of the assessment 
window; revisions were 
made to harmonize 
assessment across treatment 
arms where possible.
1.3 Schedule of Activities 
(SoA), Tables 2, 3, and 4
Timing of Quantitative immunoglobulins, 
SPEP and UPEP procedures to be conducted 
on Day 1 of Cycles 1 to 8 (Table 2) and 
Cycles 1 and 2 (Table 3) was revised to note 
an assessment window of ‘(±7 days starting 
with Cycle 2)’.
The timing for the conduct of the
aforementioned evaluations on Day 1 of 
Cycles 9 and beyond (Table 2) and for 
Cycles 3-6 and Cycles 7 and beyond (Table 3) 
was revised for an assessment window of ‘(±7 
days)’.
Timing of the Serum FLC and SIFE/UIFE 
assessment was revised in Tables 2 and 3 to 
note an assessment window of ‘(±7 days 
starting with Cycle 2)’.
In Table 4 a window of ‘(±7 days)’ was added
for the assessment of SPEP, UPEP, Serum FLC 
and SIGE/UIFE.
Clarification of timing and 
extension of assessment 
window.
1.3 Schedule of Activities 
(SoA), Tables 2 and 3
For Bone marrow aspirate and core biopsy, 
deleted the following: “To confirm CR 
(including sCR) and at the time of PD. A 
portion of aspirate collected at PD should be 
sent to the central laboratory.:
Also deleted from Notes: “Send fresh 
aspirate samples to central laboratory 
(Section 8.1.4).”
A bone marrow sample at the 
time of PD is only needed for 
subjects in Arm B
1.3 Schedule of Activities 
(SoA), Tables 2 and 3
For MRD (bone marrow aspirate) 
assessment, a cross-reference to the footnote 
stating ‘A scheduled timepoint will not be 
collected if a bone marrow aspirate for 
central MRD evaluation was performed 
within the last 3 months of that timepoint.’
was added for sample collection at time of 
suspected CR or sCR.
Clarification

JNJ-68284528 (ciltacabtagene autoleucel)
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Status: Approved,  Date: 18 August 2022
Section Number
and Name
Description of Change
Brief Rationale
1.3 Schedule of Activities 
(SoA), Tables 2, 3
Reporting of adverse events and concomitant 
therapy will be extended until ‘30 days after 
last dose or until the start of subsequent anti-
myeloma therapy, whichever is earlier’.
Extension of reporting 
period.
1.3 Schedule of Activities 
(SoA), Table 5
Additional language was added to Table 5 
regarding reporting of non-serious, all serious, 
and delayed AEs until EOS.
Clarification
1.3 Schedule of Activities 
(SoA), Table 4
Timing for Physical examination and ECOG 
procedures was revised to indicate that the 
assessment window during apheresis will be 
‘(≤72 hrs prior to apheresis)’.
Clarification of timing.
1.3 Schedule of Activities 
(SoA), Table 4
Plasmacytoma assessment in Arm B, prior to 
JNJ-68284528 infusion, revised to state 
assessment by physical exam (not by PET/CT)
Assessment by radiology 
does not occur until Day 84
1.3 Schedule of Activities 
(SoA), Table 4
Notes regarding the assessment of vital signs
were updated to state that vital signs can be 
omitted on days where bortezomib or 
daratumumab administration is planned to be 
omitted.
Updated notes for complete blood count 
(CBC) with differential and full metabolic 
panel to indicate that if bortezomib or 
daratumumab administration is planned to be 
omitted, both CBC and chemistry assessments 
on those days can be done locally but need to 
be reviewed by the Investigator.
To minimize the need for 
patients to travel to the site.
1.3 Schedule of Activities 
(SoA), Table 5
Removed “At 6 months (D196) post CAR T 
infusion (unless done w/n last 3 months (bone 
marrow aspirate).”
Also clarified that the bone marrow biopsy 
and aspirate to confirm CR is for the local lab.
The D196 bone marrow 
aspirate is for flow cytometry 
and CyTOF not disease 
assessment. 
1.3 Schedule of Activities 
(SoA), Table 4;
6.1.5.2 Criteria for Apheresis
Edits/footnotes added to indicate that blood 
samples for immunophenotyping and flow PK 
CAR+ T cells, and CyTOF/PBMC 
(TCRSeq)/plasma will be recollected prior to 
the second apheresis.
To provide instruction on
blood sample collection for 
biomarker assessment for 
subjects requiring a repeat 
apheresis. 
2.3 Benefit-Risk Assessment
Removed footnote ‘a’ from TLS in Table 6.
TLS is no longer an adverse 
event of special interest
6.1.5.3 Conditioning Regimen
Revised to note cilta-cel administration will
follow directions described in the cell therapy 
product procedures manual (CTPPM), and not 
the site investigational product procedures 
(SIPPM).
Revised for administrative 
purposes and clarity.
Revised to clarify the product release criteria, 
including instruction that ‘Products provided 
through this exceptional release or similar 
process that exceed the protocol maximum 
dose will not qualify for overdose 
reporting’.
6.1.1 Dexamethasone
Instruction added for the administration of 
dexamethasone in subjects on Arm A receiving 
dexamethasone as part of the standard therapy 
PVd.
To clarify timing and doses 
of oral dexamethasone to be 
administered to subjects 

JNJ-68284528 (ciltacabtagene autoleucel)
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Status: Approved,  Date: 18 August 2022
Section Number
and Name
Description of Change
Brief Rationale
≤75 years of age or >75 years
of age.
6.1.5.1 Apheresis and Bridging 
Therapy
Added ‘If for logistical reasons apheresis 
cannot be performed 3-6 days after 
randomization, shorter timeframe will be 
accepted when possible.’
Clarification
6.1.5.4 Criteria for 
Conditioning Regimen 
(Cyclophosphamide and 
Fludarabine) Dosing
Text updated to note that prior to the start of the 
conditioning regimen, subjects may not have 
received:
!
Dexamethasone within 7 days
!
No live, attenuated vaccines within 6 weeks 
Updates were made for 
changes in the conditioning 
regimen and for alignment 
with other sections of the 
protocol.
6.5.3 Prohibited Therapies
Updated text for Arm B to note:
!
Corticosteroid use is to be avoided after the 
start of lymphodepletion and prior to Day 
112
!
No vaccination with live, attenuated 
vaccine #6 weeks before starting the
conditioning regimen
Updated for safety concerns 
and to maintain consistency 
both within the protocol and 
with other studies in the 
program.
6.6.2 Pomalidomide and 
Bortezomib Dose Modification 
for Hematologic Toxicity;
6.6.4 Pomalidomide and 
Daratumumab Dose 
Modification for Hematologic 
Toxicities
Updated guidance on dose modification for 
pomalidomide
and/or 
bortezomib
and 
daratumumab.
Updated to address dose 
delays/skipped doses.
6.1.6.6 
Hypogammaglobulinemia
Section updated to note that:
!
Subjects with IgG <400 mg/dL or
recurrent infections (including HBV 
reactivation) should be considered for 
prophylactic IV or SC IgG as per 
institutional guidelines.
!
Vaccination with live attenuated virus 
vaccines is not permitted for at least 6 
weeks prior to the start of the 
conditioning regimen
Revised for consistency with 
other studies in the program
6.1.6.8. Hypersensitivity 
Reactions
Ampicillin was deleted.
1.3 Schedule of Activities 
(SoA), Table 5
Table revised to indicate that handwriting 
analysis will be collected on Day 56. 
Starting from Day 84, handwriting analysis 
will be performed every 28 days up to and 
including Day 196.
Clarification regarding 
timing.
1.3 Schedule of Activities 
(SoA), Table 5;
8.2.4 Clinical Safety 
Laboratory Assessments;
10.2 Appendix 2: Clinical 
Laboratory Tests
Added the laboratory assessment ‘CD4/CD8 
Lymphocyte panel’.
Safety assessment added as 
certain opportunistic 
infections are common in 
patients with low CD4 count
counts.
1.3 Schedule of Activities 
(SoA), Table 5
Additional assessment of CAR-T chemistry 
will be performed at Days 84 and 112.
Safety parameter added in 
order to closely monitor 
patients after cilta-cel 
administration.
1.3 Schedule of Activities 
(SoA), Table 5
Bone marrow core biopsy at Day 56 was 
deleted.
Typo correction and 
clarification of repetitive text.

JNJ-68284528 (ciltacabtagene autoleucel)
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Status: Approved,  Date: 18 August 2022
Section Number
and Name
Description of Change
Brief Rationale
Text regarding the collection of bone marrow 
assessment and core biopsy samples for Day 84 
through Day 196 was revised.
10.2 Appendix 2: Clinical 
Laboratory Tests
The list of laboratory tests was updated; 
changes included additions to the list of CAR-
T Chemistry assessments (ie, triglycerides and 
fibrinogen), and Tests at Screening only (ie, to 
clarify Hepatitis C virus (HCV) infection).
Safety parameter added to 
closely monitor patients after 
cilta-cel administration.
1.3 Schedule of Activities 
(SoA), Table 5
The laboratory assessment ‘Full Metabolic 
Panel’ was deleted.
Deleted as redundant; the 
CAR-T chemistry assessment 
evaluates the same 
parameters as the full 
metabolic panel, as well as 
additional parameters that aid 
in the diagnosis and 
monitoring of 
hemophagocytic 
lymphohistiocytosis (HLH). 
1.3 Schedule of Activities 
(SoA), Table 5
Flow cytometry and CyTOF instructions for 
the period of Day 35 to 196 were updated to for
collection ‘at time of suspected CR/sCR’.
Clarification of timing
1.3 Schedule of Activities 
(SoA), Table 5
The following footnote (m) was added for PK 
CAR Transgene levels:
‘After Day 112, CAR transgene levels, and 
CAR+ T cell counts will be measured every 
8 weeks through 1 year. After 1 year, PK 
CAR transgene levels and CAR+ T cell 
counts (immunophenotyping) will be 
measured at least annually until EOS or 
PD, whichever is earlier. Additional event-
triggered testing for PK CAR transgene 
levels and CAR+ T cell counts may be 
conducted as clinically indicated.’
Footnote ‘m’ also added as a cross reference 
to Immunophenotyping (whole blood)
Text added to clarify CAR 
transgene sampling 
conditions in alignment with 
FDA guidance.
6.1.5.7 JNJ-68284528 
Administration
Clarification of cilta-cel administration 
criteria, including information on the quantity 
of the dose, and dosing instructions (ie, units 
of weight).
Revised for clarity and to be 
consistent with other studies 
in the program.
8 Study Assessments and 
Procedures (Overview)
Updated the approximate blood volume to be 
collected from each subject.
Blood volume updated to 
reflect changes
7.1.2 Discontinuation of Study
Treatment for Arm B
Text added to include ‘signs of active 
infection’ as a reason for discontinuation.
Update made to align 
discontinuation criteria with 
that noted in Section 6.1.5.5.
9.4.4 Safety Analyses;
10.4 Appendix 4: Adverse 
Events: Definitions and 
Procedures for Recording, 
Evaluating, Follow-up, and 
Reporting, Severity Criteria
A paragraph was added regarding the 
summarization and grading of both CRS and 
CAR-T cell-related neurotoxicity, their
individual symptoms, and neurotoxicity not 
temporally associated with CRS or any other 
neurologic AEs that do not qualify as ICANS.
Text added to clarify grading 
and to note that the analysis 
of adverse events for CRS 
and neurotoxicity will 
separate the symptoms.
2.2.5 Summary of Nonclinical 
and Clinical Studies;
2.3 Benefit-Risk Assessment;
6.1.6.2.2 Other Neurotoxicities
Updated section with (or provided cross-
reference to) current safety and efficacy data. 
Updated based on current 
clinical data and to align with 
other studies in the program.

JNJ-68284528 (ciltacabtagene autoleucel)
Clinical Protocol 68284528MMY3002 Amendment 4
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 18 August 2022
Section Number
and Name
Description of Change
Brief Rationale
10.4 Appendix 4: Adverse 
Events: Definitions and 
Procedures for Recording, 
Evaluating, Follow-up, and 
Reporting, Severity Criteria, 
Special Reporting Situations
Instruction added on the assessment, 
reporting, and monitoring of special reporting 
situations, including those that meet the 
criteria of an adverse event (including serious 
adverse events ∃SAEs%) and death not related 
to progressive disease (PD).
Clarification of reporting and 
monitoring procedures.
6.1.6.3 Tumor Lysis Syndrome
Deleted tumor lysis syndrome as an adverse 
event of special interest (AESI).
Clarification of AESIs.
6.1.6.4 Second Primary 
Malignancy
Noted that that second primary malignancies 
(SPMs) on both arms of the study will be 
AESIs.
Clarification of AESIs.
8 Study Assessments and 
Procedures
Section updated with the following revisions: 
!
‘Local laboratory data may be collected if 
central laboratory data is not available at 
a particular timepoint, (Section 8.1.6),
however, this does not include screening 
assessments.’
!
The list of study specific materials was 
updated: ‘IPPI/SIPPM (now known as 
CTPPM)’
!
Revised sentence in Apheresis (Arm B 
only):
‘Apheresis should be performed 
according to institutional standards, with 
a collection target of 6 x 109 PBMCs 
(range: 2 to 20 x 109 PBMCs); 2 apheresis 
collections may be performed to attain 
this target. Instructions for processing and 
shipping apheresis product are provided 
in the SIPPMCTPPM.’
!
Added the following sentences to 
Treatment Phase-Bridging therapy, 
Conditioning Regimen, and 
JNJ-68284528 Administration (Arm B): 
‘Cycles beyond Bridging Cycle 1 may 
be truncated to allow for adequate 
washout and minimize time off 
therapy.’
‘Prior to dosing with JNJ-68284528, 
review of safety assessments and 
disease characteristics should be 
completed per Section 6.1.5.5.’
!
Revised sentence in Post-infusion Follow-
up Phase and Post-treatment Follow-up 
Phase (Arm B): ‘In addition, assessment 
for other delayed AEs, and assessment
yearly until assessment for RCL will be 
collected yearly until end of study and 
will continue to be collected yearly until
for up to 15 years after the 
JNJ-68284528 administration in a 
Updated to maintain 
consistency within the 
protocol and with other 
studies in the program.

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Status: Approved,  Date: 18 August 2022
Section Number
and Name
Description of Change
Brief Rationale
separate long-term follow-up study 
(Study 68284528MMY4002).’
8.1.2 Imaging
Text revised as follows: 
!
‘Positron emission tomography (PET)/CT 
with diagnostic CT component. If a CT 
scan is used it must be of diagnostic 
quality (see the disease response criteria 
in Section10.7).‘
!
‘If cross sectional iImaging reports was 
obtained, images must be made available 
to sponsor for central team review upon 
request.’
Additional instructional text was added to note 
that de-identified imaging reports (where 
permitted by local regulations) should be sent 
to the sponsor for review.
Updated to clarify imaging 
requirements.
8.1.3 Documentation of Soft 
Tissue Plasmacytomas
Text was revised to note imaging requirements 
(ie, remediation steps for poor quality CT, 
method 
documentation, 
and 
report 
availability).
Additional changes were made to note that 
‘Assessments will continue every 4 weeks or 
every 12 weeks
until development of 
confirmed 
CR 
or 
confirmed 
disease 
progression as long as the soft tissue 
plasmacytoma remains measurable on physical 
or radiological examination.’
Clarification of imaging and 
documentation requirements.
8.1.4 Bone Marrow 
Examination
Identified alternative analyses to be used in 
case of issues with sample availability or 
quality (ie, cytogenetics from central lab, 
diagnostic results from FISH analysis). 
Clarification
8.1.5 Minimal Residual Disease 
Evaluations
Added text that bone marrow evaluations 
aimed at MRD detection do not need to be 
continued if a clone for MRD detection cannot 
be identified. 
Clarification of next steps in 
case of issues with MRD 
detection.
8.1.6 Local Laboratory 
Assessments
Text added to clarify the role of central versus 
local labs (ie, preference/precedence for central 
lab collection).
Revised to provide 
direction/alternatives and 
clarify preference.
4.4 End of Study Definition
Section revised to note that all subjects who 
received JNJ-68284528 may participate in a 
long-term follow-up study; information on 
transition and monitoring was provided.
Text was added to allow the 
transition of subjects from 
MMY3002 to the LTFU 
study MMY4002.
6.8 Intervention After the End 
of the Study
Text modified to note delayed AEs will be an 
additional parameter assessed in the long-term 
follow-up study. 
Clarification
7.2 Subject 
Discontinuation/Withdrawal 
from the Study
Added text that a subject who declines to 
continue study treatment hasn’t necessarily 
withdrawn consent.
Clarification of withdrawal 
of consent.

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Clinical Protocol 68284528MMY3002 Amendment 4
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Status: Approved,  Date: 18 August 2022
Section Number
and Name
Description of Change
Brief Rationale
6.1.5.5 Evaluation Prior to 
Administration of 
JNJ-68284528
Provided information on and cross-reference 
to safety monitoring and reporting procedures 
for subjects in Arm B who have confirmed PD 
after bridging therapy and have proceeded 
forward with JNJ-68284528 infusion.
Clarification
10.6 Appendix 6: Hepatitis B 
Virus Screening
Text was added to specify when HBV-DNA 
and AST/ALT laboratories should be 
performed.
Clarifications were made in 
alignment with the SOA.
10.28 Appendix 28: Anti-
microbial Prophylaxis 
Recommendations
Information on recommended anti-microbial 
prophylaxis therapies was updated; changes 
included revisions to timing (ie, start and stop) 
and the inclusion of pentamidine as a 
treatment for Pneumocystis Pneumonia (PCP).
Update/clarification.
8.3.6 Anticipated Events
Text on the reporting of anticipated events 
was updated (ie, added cross-reference to 
instructions on reporting; provided a reminder 
of differing regulatory reporting 
requirements). 
Provided clarification on the 
reporting of anticipated 
events.
10.30 Appendix 30: Adverse 
Event Reporting Guidance for 
Study 68284528MMY3002
Appendix added. 
To provide guidelines for the 
reporting of AEs and 
expedited reporting.
8.3.1 Time Period and 
Frequency for Collecting 
Adverse Event and Serious 
Adverse Event Information
Provided updates for AE reporting in Arm B 
(ie, clarified timing and AEs to be reported 
until the end of the study, deleted information 
on the reporting of events of 
neurotoxicity/existing neurologic AEs, AESIs 
and SPMs; provided cross-reference to 
Section 10.30 for additional guidance).
To be consistent with FDA 
guidance regarding long term 
follow-up of patients after 
CAR-T dosing.
8.3.1 Time Period and 
Frequency for Collecting 
Adverse Event and Serious 
Adverse Event Information;
8.3.7 Adverse Events of 
Special Interest
Information on delayed AEs was added to 
Section 8.3.1.
Section 8.3.7 was deleted. Text for AESIs 
updated and moved to Section 8.3.1, and 
Section 8.3.1 reorganized so that information 
on all AEs is provided before that on AESIs, 
delayed AEs, and serious AEs.
Readability; updated to 
provide information about 
AE reporting in one section 
in a logical order of 
presentation.
8.2 Safety Assessments
Physical examination findings will include 
findings from neurologic exams.
Clarification regarding safety 
assessments measured.
8.4 Treatment of Overdose
Provided cross-reference to product 
information, direction on dosing, and 
instruction on product evaluation if the 
maximum dose is exceeded.
Clarifications added 
2.2.6.2 Daratumumab, 
Pomalidomide, and 
Dexamethasone
4.2.1 Study-Specific Ethical 
Design Considerations
Information was updated for 
Study 54767414MMY3013 (APOLLO). 
To provide updated 
information for comparator 
agents (ie, daratumumab in 
combination with 
pomalidomide and 
dexamethasone ∃DPd%).
6.1.6.1. Management of 
Cytokine Release Syndrome
Minor updates were made (ie, for verbiage, 
Study MMY2001 results).
Text was further updated to note that 
laboratory testing conducted for cases of 
Revised for alignment with 
other studies in the program.

JNJ-68284528 (ciltacabtagene autoleucel)
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Status: Approved,  Date: 18 August 2022
Section Number
and Name
Description of Change
Brief Rationale
severe CRS may reveal high serum levels of 
triglycerides.
8.9.2 High-risk Classification 
by Cytogenetics
Amp 1q was added to the list of specific 
molecular subgroups.
Information update.
1.3 Schedule of Activities 
(SoA), Table 4
The table title was revised.
To clarify that the treatment 
phase in Arm B is: ‘SBCM 
and Bridging Therapy’.
6.1.6.5 Prolonged Cytopenia
The section title was revised from ‘Cytopenia’ 
to ‘Prolonged Cytopenia’.
Clarification
6.1.6.7 Serious Infections
The section title was revised from ‘Infections’ 
to ‘Serious Infections’
Clarification
Title page;
1.1 Synopsis;
2 Introduction
Added generic name (cilta-cel) to the 
document and removed JNJ-68284528.
Added generic name
Throughout the protocol
Minor grammatical, formatting, or spelling 
changes were made.
Additional minor changes included:
!
The replacement of ‘JNJ-68284528’ with 
‘cilta-cel’ in any new areas of text.
!
Revision of ‘extramedullary 
plasmacytomas’ to ‘plasmacytomas’ or 
‘soft tissue plasmacytomas’
!
CTPPM has been added.
!
References to the Attachments added in 
the relevant sections.
!
The study number of the long-term follow-
up study was added as applicable.
Minor errors were noted, and 
additional minor 
clarifications/edits made

JNJ-68284528 (ciltacabtagene autoleucel)
Clinical Protocol 68284528MMY3002 Amendment 4
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 18 August 2022
Amendment 1 (20 March 2020)
Overall Rationale for the Amendment: To add other neurotoxicities as a safety risk and implement 
additional monitoring and risk minimization measures for JNJ-68284528.
Section number
and Name
Description of Change
Brief Rationale
Title Page
Study number was corrected to remove the JNJ-
prefix:
JNJ 68284528MMY3002
Correction of error
1.3. Schedule of 
Activities
For Arm B in Table 5, collection of a 
handwriting sample and frequency of testing was 
added to the study procedures. Study Day 35 and 
Day 42 were added to the table as additional 
assessment days for collection of handwriting 
samples.
Update of safety information to 
include other neurotoxicities
For Arm B in Table 5, extend ICE neurologic 
test to be performed at least daily until ICANS
is resolved.
For Arm B in Table 5, Reporting of neurologic 
adverse events or exacerbation of existing
neurologic adverse events will be extended to up 
to 12 months after JNJ-68284528 infusion
2.2.5. Summary of 
Nonclinical and Clinical 
Studies
Added to summary of data for Study 
68284528MMY2001 a description of 6 cases of 
other neurotoxicities.
2.3. Benefit-Risk 
Assessment
Added other neurotoxicities to Table 6 (Risks 
Associated with JNJ-68284528 and Mitigation 
Strategies) as a subsection of neurological 
adverse events
3. Objectives and 
Endpoints
Added exploratory objective and endpoints to 
characterize potential early predictive markers 
for neurotoxicity
5.2. Exclusion Criteria
Revised Criterion #18 to add:
Any history of Parkinson’s disease or other 
neurodegenerative disorder
6.1.6.2. Neurologic 
Adverse events
Divided section into overall neurologic adverse 
events with sub-sections of CAR-T cell related 
neurotoxicity (ICANS) (Section 6.1.6.2.1) and 
other neurotoxicities (Section 6.1.6.2.2)
6.1.6.2.1. CAR-T Cell-
related Neurotoxicity 
(ICANS)
Added “Consider performing neuroimaging (eg, 
MRI)…”
Clarified that hospitalization is required for 
Grade 2, 3, or 4 CAR-T cell-related 
neurotoxicity temporally associated to CRS.
Added recommendation to rule out alternative 
etiologies at first sign of neurotoxicity.
Table 12 (Guidelines for Management of 
ICANS) – added to row 1 (ICE score 7-9) when 
no concurrent CRS dexamethasone can be 
considered
6.1.6.2.2. Other 
Neurotoxicities
New section with guidance to monitor for other 
neurotoxicities
8.2.7. Neurologic 
Examination
Added the following:

JNJ-68284528 (ciltacabtagene autoleucel)
Clinical Protocol 68284528MMY3002 Amendment 4
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 18 August 2022
Section number
and Name
Description of Change
Brief Rationale
For subjects with prior pertinent neurologic 
disease (eg, stroke, encephalitis) consider 
baseline MRI of the brain and an EEG.
8.2.7. Neurologic 
Examination;
8.3.1. Time Period and 
Frequency for Collecting 
Adverse Event and 
Serious Adverse Event 
Information
Added a section describing the assessment for 
qualitative changes in handwriting.
8.3.1. Time Period and 
Frequency for Collecting 
Adverse Event and 
Serious Adverse Event 
Information
Text updated to include additional guidance 
regarding the reporting of neurotoxicity events.
10.27: Appendix 27: 
Table for added for qualitative grading of 
handwriting sample
1.3. Schedule of 
Activities
Table 1, Screening Phase for All subjects, 
Hepatitis B recommendation revised as follows:
HBsAg, anti-HBc, anti-HBs, HBV DNA 
quantification (for subjects who are anti-HBs 
positive without history of vaccination or for 
subjects who are anti-HBc positive with or 
without anti-HBs positive and anti HBc 
positive).
For Arm A Table 2, Arm A Table3, and Arm B 
Table 5, Added “For subjects at risk for HBV 
activation, monitor HBV DNA and AST/ALT
every 12 weeks (±7 days) until 1-year post-dose 
of JNJ-68284528” to HBV-DNA row.
Revisions to enrich the clinical 
trial population by allowing 
inclusion of subjects who are 
anti-HBc positive with or 
without anti-HBs positive
5.2. Exclusion Criteria
Revised criterion #17 (bullet ‘b’) to state 
“Subjects who are anti-HBs positive and without 
history of vaccination or for subjects who are 
anti-HBc positive with or without anti-HBs 
positive and anti HBc positive” should have 
HBV DNA quantification test done.
10.2. Appendix 2: 
Clinical Laboratory Tests
Revisions made to Hepatitis B serology:
Hepatitis B: HBsAg, anti-HBc, anti-HBs, HBV 
DNA quantification (for subjects who are anti-
HBs positive without history of vaccination or 
for subjects who are anti-HBc positive with or 
without anti-HBs positive and anti HBc 
positive)
10.6. Appendix 6: 
Hepatitis B Virus 
Screening
Revised hepatitis B screening guide to allow 
subjects who are anti-HBc positive only to 
participate in the study 
Added “If there is evidence of HBV reactivation 
initiate treatment as appropriate per institutional 
guidance”.
1.3. Schedule of 
Activities
For Arm B, Table 5 moved MRD testing from 
Day 28 to Day 56
Change to align MRD testing 
with timing that is more 
clinically meaningful  
CCI

JNJ-68284528 (ciltacabtagene autoleucel)
Clinical Protocol 68284528MMY3002 Amendment 4
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 18 August 2022
Section number
and Name
Description of Change
Brief Rationale
1.3. Schedule of 
Activities
Bone marrow aspirate and core biopsy 
requirement for Arm A in Table 2 and Table 3 
was changed to reflect a portion of the aspirate 
collected at PD should be sent to the central 
laboratory. 
Revised for clarity
1.3. Schedule of 
Activities
For Arm A Table 2 (PVd), Table 3 (DPd) and 
Arm B Table 5: MRD (bone marrow aspirate) 
required of all dosed subjects at defined 
timepoints regardless of status and for subjects 
with suspected CR, at the time of CR and then 
yearly for subjects that remain on study up to 
PD.
1.3. Schedule of 
Activities
For Arm A, footnote “a” for Table 2 and Table 3 
was updated with the following text 
“Assessments and procedures on Cycle 1 Day 1 
to be performed prior to administration of study 
intervention.”
1.3. Schedule of 
Activities
For Arm B, Table 4, infectious disease testing 
during the Apheresis phase of the study will be 
performed for other countries as required by 
country or per local regulations
1.3. Schedule of 
Activities
For Arm B, Table 4, added the following to 
footnote “a”:  Safety laboratory assessments may 
be performed prior to initiating bridging therapy.
1.3. Schedule of 
Activities
For Arm B, Table 4, added footnote “c” to 
Apheresis heading stating that “Assessments and 
procedures to be performed prior to apheresis”
1.3. Schedule of 
Activities
For Arm B in Table 5, the frequency of CBC 
with differential was updated to every 12 weeks 
(=/- 7 days) on 2 occasions and then every 6 
months (+/- 14 days) until PD or EOS, 
whichever is earlier. 
1.3. Schedule of 
Activities
For Arm B in Table 5, the bone marrow aspirate 
and core biopsy requirement was updated to “At 
time of PD or and EOS (bone marrow biopsy 
and aspirate)”. Also added that bone marrow 
biopsy should be obtained at PD and sent to the 
central laboratory.
1.3. Schedule of 
Activities
For Arm B in Table 5, the footnote ‘l’ was added 
for Immunophenotyping
1.3. Schedule of 
Activities
For Arm B in Table 5, PK CAR transgene 
samples, soluble BCMA samples, and 
immunogenicity samples will be collected at PD 
or EOS.
1.3. Schedule of 
Activities
For Arm B in Table 5 footnote ‘d’, provision of 
window at end of infusion for vital signs was 
deleted
2.3. Benefit-Risk 
Assessment
Added guidance to CRS and neurologic adverse 
events to “Notify the sponsor if subject is 
experiencing Grade 2 or higher CRS”.
5.1. Inclusion Criteria
Revised inclusion criterion 6 to clarify definition 
of refractory to lenalidomide, to include failure 
to achieve minimal response.

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Status: Approved,  Date: 18 August 2022
Section number
and Name
Description of Change
Brief Rationale
5.2. Exclusion Criteria
Revised exclusion criterion 10 to provide 
guidance to subjects with contraindications to 
DPd or PVd.
6.1. Study Interventions 
Administered
Formatting change to Table 8 to add a row titled 
“Either DPd or PVd followed by”
Revised table footnotes to provide guidance if 
additional cycles are indicated
6.1.2. Bortezomib
Added guidance for consideration of additional 
cycles of bridging therapy
6.1.5.7. JNJ-68284528 
Administration
Clarified in hospitalization requirements in 
Table 10 that hospitalization is required for 
Grade 2, 3, or 4 ICANS temporally associated 
to CRS.  Added that hospitalization for 
neurotoxicity that is not temporally associated 
with CRS is at the discretion of the investigator.
6.2.1. Accountability
Added clarification that information in this 
section relates to study treatment that is supplied 
to investigational sites from the sponsor.
6.5. Concomitant 
Therapy
Revised concomitant chemotherapy entry as 
follows:
Chemotherapy (including any given for CAR-T 
cell related toxicity HLH)
6.5.2. Permitted 
Medications
Added that chemotherapy agents used to treat 
CAR-T cell related toxicities are permitted upon 
consultation with the sponsor.
Removed exception for therapy to treat CAR-T 
cell related toxicity from prohibited therapies in 
Section 6.5.3.
6.6.1. Dexamethasone
Clarified statement that for subjects whose 
dexamethasone treatment is discontinued, they 
may continue to receive 
pomalidomide/bortezomib or 
daratumumab/pomalidomide
8.1.4. Bone Marrow 
Examination
Clarified that portion of bone marrow aspirate to 
be sent to central laboratory for 
immunophenotyping and to monitor BCMA is 
specific to subjects in Arm B.
8.1.5. Minimal Residual 
Disease Evaluations
Clarification of collections for MRD
8.3.6. Anticipated Events
Moved Anticipated Events into its own section 
(from Section 8.3.5) as it is not a regulatory 
reporting requirement for all countries
8.3.1. Adverse Events of 
Special Interest
Added other neurotoxicities
8.5.3. Pharmacokinetic 
Parameters and 
Evaluations
Clarification to existing text.
8.9. Biomarkers
Defined that additional biomarker samples 
include but are not limited to serum or PBMCs 
from whole blood. 
Clarified that a tumor sample should be 
collected from subjects in Arm B diagnosed with 
a SPM.

JNJ-68284528 (ciltacabtagene autoleucel)
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Status: Approved,  Date: 18 August 2022
Section number
and Name
Description of Change
Brief Rationale
8.9. Biomarkers
Added that if a subject dies and an autopsy is 
preformed, specimens may be requested by the 
sponsor for analysis.
9.3. Populations for 
Analysis
Safety analysis set consists of All randomized 
subjects who received at least one dose any part
of study treatment.
9.4.6. Biomarkers 
Analyses
Clarified that core biopsy sample from bone 
marrow biopsy performed at disease progression 
should be sent to the central laboratory.
1.3. Schedule of 
Activities
For Arm B in Table 5, post-infusion follow-up 
assessment Days revised: Day 8 assessment 
changed to Day 7 and Day 22 assessment 
changed to Day 21
Revised for consistency with 
other studies in the program
1.3. Schedule of 
Activities
For Arm B in Table 5, removed post end of 
infusion collections for PK CAR transgene 
levels sample and soluble BCMA sample.
Reduction in sample collection
1.3. Schedule of 
Activities;
8.1.6. Local Laboratory 
Assessments;
8. Study Assessments and 
Procedures;
8.1. Efficacy 
Assessments;
8.1.1. Myeloma Protein 
Measurements in Serum 
and Urine
Table 2 (footnote d), Table 3 (footnote e), Table 
4 (footnote d), Table 5 (footnote o): Added that 
local laboratory assessments may be used under 
specified circumstances.
Guidance added that all efforts should be made 
to collect efficacy data centrally, however local 
data may be collected if central data is not 
available at a particular time point.
Revisions to allow for flexibility 
in collecting laboratory data
1.3. Schedule of 
Activities
Dexamethasone treatment in Table 3 revised for 
clarity to state “Days 1, 8, 15, and 22 of each 28-
day cycle”
Correction of error
For Arm B in Table 5, Assessment of 
plasmacytomas by physical examination if 
applicable was added at the time of conditioning 
regimen. Footnote “n” added to indicate that the 
assessment should occur as close to prior to the 
first dose as possible.
4.4. End of Study 
Definition
Correction made to the study completion 
definition:
A subject will be considered to have completed 
the study if he or she has either died before the 
end of the study, is not lost to follow-up, has not
withdrawn consent for study participation or 
study terminated by sponsor.
6.1.6.1. Management of 
Cytokine Release 
Syndrome
In second row of Table 11, footnote for low-
flow nasal cannula was corrected from “a” to 
“d”.
6.5.1.3. Prophylaxis for 
Infections
Prophylaxis to prevent herpes zoster reactivation 
should continue for at least 3 months 6 months
following last dose of study treatment.

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Status: Approved,  Date: 18 August 2022
Section number
and Name
Description of Change
Brief Rationale
8.12 Medical Resource 
Utilization and Health 
Economics
Deleted the statement “Health Economics 
parameters are not evaluated in this study” and 
added “All health economic data will be used 
only in a de-identified manner”.
Added “Health economics data such as
medical resource utilization data associated with 
medical encounters….”
10.2. Appendix 2: 
Clinical Laboratory Tests
Correction made to Laboratory Assessments: 
“Tests within 60 days prior to apheresis
randomization”
10.4 Appendix 4: 
Adverse Events
Daratumumab safety information reference 
changed from PI or SmPC to IB
2.3. Benefit-Risk
Assessment
Removed statement “Clinical experience with 
JNJ-68284528 and LCAR-B38M CAR-T cells is 
limited” as to date almost 100 subjects have 
received an infusion of JNJ-68284528
Update based on current clinical 
data
2.3. Benefit-Risk 
Assessment;
6.1.6.7. Infections
Added that JNJ-68284528 should not be 
administered to subjects with active infections
Added recommendation for extended use of anti-
microbial therapies
Revised guidance for infections
10.28. Appendix 28 
(Anti-microbial 
Prophylaxis
Added table with anti-microbial prophylaxis 
recommendations
3. Objectives and 
Endpoints
Added a separate secondary endpoint for time to 
worsening of symptoms as captured by the 
MySIm-Q total symptoms score (separate from 
the overall PRO endpoints) as it is defined 
specifically in Section 9.4.3.
Revision for consistency
6.1.2. Bortezomib
Additional cycles of bridging therapy may be 
considered based on subject’s clinical status and 
timing and availability of JNJ-68284528
Addition of guidance for the 
consideration of bridging therapy
6.1.3. Daratumumab
Additional cycles of bridging therapy may be 
considered based on subject’s clinical status and 
timing and availability of JNJ-68284528
6.1.5.1. Apheresis and 
Bridging Therapy
Additional cycles of bridging therapy may be 
considered based on subject’s clinical status and 
timing and availability of JNJ-68284528
6.1.5.5. Evaluation Prior 
to Administration of JNJ-
68284528
Language added to allow for subjects with 
confirmed PD after bridging therapy to receive 
JNJ-68284528 after consultation with the 
sponsor and evaluation of risks and benefits to 
the subject.
Addition to allow for subjects 
with confirmed PD after bridging 
therapy to receive JNJ-68284528 
if requested by investigator
6.2.5. Cytopenia
Added consideration of parvovirus B19 
monitoring
Additional guidance for 
cytopenia and 
hypogammaglobulinemia
6.2.6. 
Hypogammaglobulinemia
Added that subjects IG <400 mg/dL and 
recurrent infections may receive prophylactic 
IVIG
6.8. Intervention After 
the End of the Study
Revised language to state that subjects 
benefiting from treatment will be able to 
continue treatment after the end of study.
Revision to be consistent with 
Janssen policy
10.12. Appendix 12: 
Contraceptive and Barrier 
Guidance and Collection 
of Pregnancy Information
Revised definition of postmenopausal as no 
menses for 24 months without an alternative 
medical cause.
Revised to be consistent with 
pomalidomide pregnancy 
prevention program

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Status: Approved,  Date: 18 August 2022
Section number
and Name
Description of Change
Brief Rationale
10.20. Appendix 20: 
Multiple Myeloma 
Symptom and Impact 
Questionnaire
Updated sample of MySIm-Q with latest version
Update to current version of 
questionnaire
6.1.6.1. Management of 
Cytokine Release 
Syndrome
Added column for CRS grade to Table 11
Grading added to CRS and 
ICANS management tables to 
reflect adoption of ASBMT 
criteria across study protocols
6.1.6.2.1. CAR-T Cell-
related Neurotoxicity 
(ICANS)
Added column for ICANs grade to Table 12
Throughout the protocol
Minor grammatical, formatting, or spelling 
changes were made.
Minor errors were noted

JNJ-68284528 (ciltacabtagene autoleucel)
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Status: Approved,  Date: 18 August 2022
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................. 22
LIST OF IN-TEXT TABLES AND FIGURES.............................................................................................. 26
1.
PROTOCOL SUMMARY ................................................................................................................... 27
1.1.
Synopsis......................................................................................................................................... 27
1.2.
Schema .......................................................................................................................................... 29
1.3.
Schedule of Activities (SoA)........................................................................................................... 30
2.
INTRODUCTION................................................................................................................................ 49
2.1.
Study Rationale.............................................................................................................................. 49
2.2.
Background .................................................................................................................................... 50
2.2.1.
Multiple Myeloma........................................................................................................................ 50
2.2.2.
B-Cell Maturation Antigen........................................................................................................... 50
2.2.3.
CAR-T Therapy........................................................................................................................... 51
2.2.4.
JNJ-68284528 ............................................................................................................................ 51
2.2.5.
Summary of Nonclinical and Clinical Studies ............................................................................. 52
2.2.6.
Comparator Agents..................................................................................................................... 55
2.2.6.1.
Pomalidomide, Bortezomib, and Dexamethasone .................................................................. 55
2.2.6.2.
Daratumumab, Pomalidomide, and Dexamethasone .............................................................56
2.3.
Benefit-Risk Assessment ............................................................................................................... 58
3.
OBJECTIVES AND ENDPOINTS ..................................................................................................... 61
4.
STUDY DESIGN ................................................................................................................................ 62
4.1.
Overall Design................................................................................................................................ 62
4.1.1.
Arm A.......................................................................................................................................... 63
4.1.2.
Arm B.......................................................................................................................................... 64
4.2.
Scientific Rationale for Study Design............................................................................................. 66
4.2.1.
Study-Specific Ethical Design Considerations ........................................................................... 66
4.3.
Justification for Dose...................................................................................................................... 67
4.3.1.
Rationale for PVd Dose Selection .............................................................................................. 67
4.3.2.
Rationale for DPd Dose Selection .............................................................................................. 67
4.3.3.
Rationale for JNJ-68284528 Dose Selection.............................................................................. 68
4.4.
End of Study Definition................................................................................................................... 68
5.
STUDY POPULATION ...................................................................................................................... 68
5.1.
Inclusion Criteria ............................................................................................................................ 69
5.2.
Exclusion Criteria ........................................................................................................................... 72
5.3.
Lifestyle Considerations................................................................................................................. 76
5.4.
Screen Failures .............................................................................................................................. 76
6.
STUDY INTERVENTION................................................................................................................... 77
6.1.
Study Interventions Administered .................................................................................................. 77
6.1.1.
Dexamethasone.......................................................................................................................... 78
6.1.2.
Bortezomib.................................................................................................................................. 79
6.1.3.
Daratumumab............................................................................................................................. 79
6.1.4.
Pomalidomide ............................................................................................................................. 79
6.1.5.
JNJ-68284528 ............................................................................................................................ 80
6.1.5.1.
Apheresis and Bridging Therapy ............................................................................................. 80
6.1.5.2.
Criteria for Apheresis............................................................................................................... 80
6.1.5.3.
Conditioning Regimen ............................................................................................................. 81
6.1.5.4.
Criteria for Conditioning Regimen (Cyclophosphamide and Fludarabine) Dosing.................. 81
6.1.5.5.
Evaluation Prior to Administration of JNJ-68284528...............................................................82
6.1.5.6.
Pre-JNJ-68284528 Infusion Supportive Therapy .................................................................... 83

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6.1.5.7.
JNJ-68284528 Administration ................................................................................................. 83
6.1.6.
Management Guidelines for Potential Risks of JNJ-68284528.................................................. 85
6.1.6.1.
Management of Cytokine Release Syndrome.........................................................................85
6.1.6.2.
Neurologic Toxicities ............................................................................................................... 88
6.1.6.2.1.
CAR-T Cell-related Neurotoxicity (Immune Effector Cell-Associated Neurotoxicity 
Syndrome [ICANS])..............................................................................................................88
6.1.6.2.2.
Other Neurotoxicities............................................................................................................ 90
6.1.6.3.
Tumor Lysis Syndrome............................................................................................................ 91
6.1.6.4.
Second Primary Malignancy.................................................................................................... 92
6.1.6.5.
Prolonged Cytopenia ............................................................................................................... 92
6.1.6.6.
Hypogammaglobulinemia........................................................................................................ 92
6.1.6.7.
Serious Infections .................................................................................................................... 92
6.1.6.8.
Hypersensitivity Reactions ...................................................................................................... 93
6.1.7.
Management Guidelines for Daratumumab................................................................................93
6.1.7.1.
Infusion-Related Reaction Management for Daratumumab SC.............................................. 93
6.1.7.2.
Infections ................................................................................................................................. 94
6.2.
Preparation/Handling/Storage/Accountability ................................................................................ 95
6.2.1.
Accountability.............................................................................................................................. 95
6.3.
Measures to Minimize Bias: Randomization..................................................................................96
6.4.
Study Intervention Compliance...................................................................................................... 96
6.5.
Concomitant Therapy..................................................................................................................... 97
6.5.1.
Recommended Medications ....................................................................................................... 98
6.5.1.1.
Prophylaxis for Thromboembolism.......................................................................................... 98
6.5.1.2.
Proton Pump Inhibitor.............................................................................................................. 98
6.5.1.3.
Prophylaxis for Infections ........................................................................................................ 99
6.5.1.4.
Pre-injection Medications for Daratumumab ........................................................................... 99
6.5.1.5.
Post-Injection Medications for Daratumumab ......................................................................... 99
6.5.1.6.
Prophylaxis for TLS ............................................................................................................... 100
6.5.2.
Permitted Medications .............................................................................................................. 100
6.5.3.
Prohibited Therapies................................................................................................................. 101
6.5.4.
Subsequent Anti-myeloma Therapy .........................................................................................102
6.6.
Dose Modification......................................................................................................................... 102
6.6.1.
Dexamethasone........................................................................................................................ 102
6.6.2.
Pomalidomide and Bortezomib Dose Modification for Hematologic Toxicity ........................... 104
6.6.3.
Pomalidomide Dose Modification Guidelines for Non-hematologic Toxicities ......................... 106
6.6.4.
Pomalidomide and Daratumumab Dose Modification for Hematologic Toxicities.................... 106
6.6.5.
JNJ-68284528 .......................................................................................................................... 108
6.7.
Follow-up for Subsequent Myeloma Therapy and Survival (Arm A and Arm B).......................... 108
6.8.
Intervention After the End of the Study........................................................................................ 108
7.
DISCONTINUATION OF STUDY INTERVENTION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL .............................................................................................109
7.1.
Discontinuation of Study Intervention .......................................................................................... 109
7.1.1.
Discontinuation of Study Treatment for Arm A .........................................................................109
7.1.2.
Discontinuation of Study Treatment for Arm B .........................................................................109
7.2.
Subject Discontinuation/Withdrawal from the Study.................................................................... 110
7.3.
Lost to Follow-up.......................................................................................................................... 111
8.
STUDY ASSESSMENTS AND PROCEDURES .............................................................................111
8.1.
Efficacy Assessments .................................................................................................................. 116
8.1.1.
Myeloma Protein Measurements in Serum and Urine..............................................................116
8.1.2.
Imaging ..................................................................................................................................... 117
8.1.3.
Documentation of Soft Tissue Plasmacytomas........................................................................ 118
8.1.4.
Bone Marrow Examination........................................................................................................ 119
8.1.5.
Minimal Residual Disease Evaluations.....................................................................................119
8.1.6.
Local Laboratory Assessments ................................................................................................ 119
8.2.
Safety Assessments..................................................................................................................... 119
8.2.1.
Physical Examinations.............................................................................................................. 120

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8.2.2.
Vital Signs................................................................................................................................. 120
8.2.3.
Electrocardiograms................................................................................................................... 120
8.2.4.
Clinical Safety Laboratory Assessments .................................................................................. 120
8.2.5.
Eastern Cooperative Oncology Group Performance Status.....................................................121
8.2.6.
Transthoracic Echocardiogram or MUGA Scan ....................................................................... 121
8.2.7.
Neurologic Examination............................................................................................................ 121
8.3.
Adverse Events and Serious Adverse Events .............................................................................122
8.3.1.
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event 
Information................................................................................................................................ 122
8.3.2.
Follow-up of Adverse Events and Serious Adverse Events ..................................................... 125
8.3.3.
Pregnancy................................................................................................................................. 125
8.3.4.
Disease-Related Events and Disease-Related Outcomes not Qualifying as Adverse 
Events or Serious Adverse Events ...........................................................................................126
8.3.5.
Regulatory Reporting Requirements for Serious Adverse Events ........................................... 126
8.3.6.
Anticipated Events.................................................................................................................... 126
8.4.
Treatment of Overdose ................................................................................................................ 127
8.5.
Pharmacokinetics (Arm B Only)................................................................................................... 127
8.5.1.
Evaluations ............................................................................................................................... 127
8.5.2.
Analytical Procedures............................................................................................................... 128
8.5.3.
Pharmacokinetic Parameters and Evaluations......................................................................... 128
8.6.
Pharmacodynamics...................................................................................................................... 128
8.7.
Pharmacokinetic/Pharmacodynamic Evaluations........................................................................ 128
8.8.
Genetics ....................................................................................................................................... 128
8.9.
Biomarkers ................................................................................................................................... 128
8.9.1.
Pharmacodynamic/Predictive Markers.....................................................................................129
8.9.2.
High-risk Classification by Cytogenetics................................................................................... 130
8.10.
Immunogenicity Assessments (Arm B Only)................................................................................130
8.11.
Patient-Reported Outcome Assessments....................................................................................130
8.12.
Medical Resource Utilization and Health Economics .................................................................. 132
9.
STATISTICAL CONSIDERATIONS................................................................................................132
9.1.
Statistical Hypotheses.................................................................................................................. 133
9.2.
Sample Size Determination ......................................................................................................... 133
9.3.
Populations for Analyses.............................................................................................................. 133
9.4.
Statistical Analyses ...................................................................................................................... 133
9.4.1.
General Considerations............................................................................................................ 133
9.4.2.
Primary Endpoint ...................................................................................................................... 133
9.4.3.
Secondary Endpoints................................................................................................................ 134
9.4.4.
Safety Analyses ........................................................................................................................ 135
9.4.5.
Pharmacokinetic Analyses........................................................................................................ 136
9.4.6.
Biomarkers Analyses................................................................................................................ 136
9.4.7.
Immunogenicity Analyses......................................................................................................... 136
9.4.8.
Pharmacokinetic/Pharmacodynamic Analyses ........................................................................ 136
9.4.9.
Patient-Reported Outcome Analyses .......................................................................................137
9.4.10.
Medical Resource Utilization .................................................................................................... 137
9.5.
Interim Analysis............................................................................................................................ 137
9.6.
Data Monitoring Committee or Other Review Board ...................................................................137
10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .......................... 137
10.1.
Appendix 1: Abbreviations ........................................................................................................... 138
10.2.
Appendix 2: Clinical Laboratory Tests ......................................................................................... 140
10.3.
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations....................................... 142
10.4.
Appendix 4: Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting............................................................................................................. 153
10.5.
Appendix 5: International Staging System................................................................................... 159
10.6.
Appendix 6: Hepatitis B Virus Screening ..................................................................................... 160
10.7.
Appendix 7: Criteria for Response to Multiple Myeloma Treatment ............................................ 161
10.8.
Appendix 8: International Myeloma Working Group Diagnostic Criteria...................................... 163

JNJ-68284528 (ciltacabtagene autoleucel)
Clinical Protocol 68284528MMY3002 Amendment 4
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Status: Approved,  Date: 18 August 2022
10.9.
Appendix 9: Prior Multiple Myeloma Therapy Lines .................................................................... 164
10.10.
Appendix 10: Eastern Cooperative Oncology Group Performance Status Score ....................... 165
10.11.
Appendix 11: Formulas for Estimating Glomerular Filtration Rate .............................................. 166
10.12.
Appendix 12: Contraceptive and Barrier Guidance and Collection of Pregnancy 
Information ................................................................................................................................... 167
10.13.
Appendix 13: Conversion Table for Glucocorticoid Dose ............................................................170
10.14.
Appendix 14: New York Heart Association Functional Classification .......................................... 171
10.15.
Appendix 15: Immune Effector Cell-associated Encephalopathy (ICE) Tool .............................. 172
10.16.
Appendix 16: JNJ-68284528 Outpatient Administration Guidelines............................................ 173
10.17.
Appendix 17: Monitoring for Subjects Receiving JNJ-68284528 as Outpatient .......................... 175
10.18.
Appendix 18: The Family of Antihistamine Medications .............................................................. 176
10.19.
Appendix 19: EORTC QLQ-C30.................................................................................................. 177
10.20.
Appendix 20: Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q)...................... 179
10.21.
Appendix 21: EQ-5D-5L............................................................................................................... 185
10.22.
Appendix 22:  Patient’s Global Impression of Severity of Multiple Myeloma............................... 188
10.23.
Appendix 23: NCI PRO-CTCAE ITEMS.......................................................................................189
10.24.
Appendix 24: Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) ASTCT 
Consensus Grading System ........................................................................................................ 191
10.25.
Appendix 25: Cytokine Release Syndrome ASTCT Consensus Grading System ...................... 192
10.26.
Appendix 26: Protocol Amendment History .................................................................................193
10.27.
Appendix 27: 
............................................ 194
10.28.
Appendix 28: Anti-microbial Prophylaxis Recommendations ...................................................... 195
10.29.
Appendix 29: Study Conduct During a Natural Disaster.............................................................. 196
10.30.
Appendix 30: Adverse Event Reporting Guidance for Study 68284528MMY3002 ..................... 200
11.
REFERENCES................................................................................................................................. 202
INVESTIGATOR AGREEMENT ............................................................................................................... 205
CCI

JNJ-68284528 (ciltacabtagene autoleucel)
Clinical Protocol 68284528MMY3002 Amendment 4
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 18 August 2022
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
Schedule of Activities for Screening Phase for All Subjects..................................................... 30
Table 2:
Schedule of Activities for Standard Therapy Treatment Arm (Arm A) (PVd): Treatment 
and Post-Treatment Follow-up Phases ....................................................................................32
Table 3:
Schedule of Activities for Standard Therapy Treatment Arm (Arm A) (DPd): Treatment 
and Post-Treatment Follow-up Phases ....................................................................................35
Table 4:
Schedule of Activities for JNJ-68284528 Treatment Arm (Arm B): Treatment Phase --
Apheresis and Bridging Therapy ..............................................................................................38
Table 5:
Schedule of Activities for JNJ-68284528 Treatment Arm (Arm B): Treatment 
(Conditioning Regimen and JNJ-68284528 Infusion), Post-Infusion Follow-up, and 
Post-Treatment Follow-up Phases ...........................................................................................41
Table 6:
Risks Associated with JNJ-68284528 and Mitigation Strategies.............................................. 58
Table 7:
Study Treatment Schedule for Standard Therapy (Arm A).......................................................77
Table 8:
Study Treatment Schedule for JNJ-68284528 (Arm B)............................................................ 78
Table 9:
Pre-JNJ-68284528 Infusion Medications.................................................................................. 83
Table 10:
JNJ-68284528 Administration................................................................................................... 84
Table 11:
Guidelines for the Management of Cytokine Release Syndrome............................................. 86
Table 12:
Guidelines for the Management of Immune Effector Cell-Associated Neurotoxicity 
Syndrome (ICANS) ................................................................................................................... 89
Table 13:
Guidelines for the Management of Raised Intracranial Pressure (ICP) / Cerebral 
Edemaa ..................................................................................................................................... 90
Table 14:
Dexamethasone Dose Reduction Steps for Subjects Receiving PVd.................................... 102
Table 15:
Dexamethasone Dose Reduction Guidelines for Subjects ≤ 75 years of Age Receiving 
DPd ......................................................................................................................................... 102
Table 16:
Dexamethasone Dose Reduction Guidelines for Subjects > 75 years of Age Receiving 
DPd ......................................................................................................................................... 103
Table 17:
Treatment Guidelines for Dexamethasone-related Toxicity ................................................... 103
Table 18: Pomalidomide and Bortezomib Dose Modification Guidelines for Hematologic Toxicity ....... 104
Table 19:
Dose Reduction Guideline for Pomalidomide Toxicity............................................................105
Table 20:
Dose Reduction Guideline for Bortezomib Toxicity ................................................................105
Table 21:
Treatment Guidelines for Bortezomib-related Neuropathy.....................................................105
Table 22:
Pomalidomide and Daratumumab Dose Modification/Dose Delay Guideline for 
Hematologic Toxicities............................................................................................................ 107
Table 23:
Daratumumab Administration Schedule ................................................................................. 107
FIGURES
Figure 1:
Schematic Overview of the Study............................................................................................. 29
Figure 2:
LCAR-B38M Coding Region..................................................................................................... 51

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Clinical Protocol 68284528MMY3002 Amendment 4
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Status: Approved,  Date: 18 August 2022
1. PROTOCOL SUMMARY
1.1.
Synopsis
A Phase 3 Randomized Study Comparing JNJ-68284528, a Chimeric Antigen Receptor T cell (CAR-T) 
Therapy Directed Against BCMA, versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or 
Daratumumab, Pomalidomide and Dexamethasone (DPd) in Subjects with Relapsed and Lenalidomide-
Refractory Multiple Myeloma
JNJ-68284528 (ciltacabtagene autoleucel [cilta-cel]) is an autologous CAR-T therapy that targets B-cell 
maturation antigen (BCMA), a molecule expressed on the surface of mature B lymphocytes and malignant 
plasma cells. Results from the Phase 1b portion of Study 68284528MMY2001 indicate that cilta-cel has 
anti-myeloma activity and a safety profile consistent with the known mechanism of action of the product. 
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary
!
To compare the efficacy of cilta-cel with 
standard therapy, either PVd or DPd
!
Progression-free survival (PFS)
Hypothesis
The primary hypothesis is that cilta-cel will significantly improve PFS compared with standard therapy 
(PVd or DPd), in subjects who have previously received 1 to 3 prior line(s) of therapy, that included a 
proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) and who are refractory to lenalidomide.
OVERALL DESIGN
This is a Phase 3, randomized, open-label, multicenter study to determine whether treatment with cilta-cel
will provide efficacy benefit compared to standard therapy (PVd or DPd) in subjects with relapsed and 
lenalidomide-refractory multiple myeloma (MM).
NUMBER OF SUBJECTS
Approximately 400 subjects will be randomized 1:1 to Arm A or Arm B:
!
Arm A: standard therapy with either PVd or DPd
!
Arm B: Cilta-cel
INTERVENTION GROUPS AND DURATION
The choice of whether the subjects will be treated with PVd or DPd as standard therapy or part of the 
bridging therapy will be determined by the investigator prior to screening and will be dependent on the 
subject’s prior exposure to anti-myeloma therapies. 
Subjects randomized to Arm A will receive PVd or DPd until confirmed progressive disease (PD), death, 
intolerable toxicity, withdrawal of consent, or end of study. Subjects who discontinue PVd or DPd for any 
reason, other than PD or withdrawal of consent, will continue to be followed for response assessment until 
confirmed PD or the start of a subsequent anti-myeloma therapy. After confirmed PD, subjects will be 
followed for survival status, subsequent anti-myeloma therapies, and the occurrence of second primary 
malignancies (SPMs) every 16 weeks until the end of the study. 

JNJ-68284528 (ciltacabtagene autoleucel)
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Status: Approved,  Date: 18 August 2022
Subjects randomized to Arm B will undergo apheresis to acquire peripheral blood mononuclear cells 
(PBMCs). Subjects will receive PVd or DPd as bridging therapy, following apheresis. After cilta-cel
production and product release, subjects will receive a conditioning regimen of cyclophosphamide and 
fludarabine. Cilta-cel will be administered 5 to 7 days after the start of the conditioning regimen. Subjects 
will have intensive monitoring for safety, pharmacokinetics, biomarkers, and efficacy during the first 
112 days after cilta-cel administration (post-infusion follow-up). During the post-treatment follow-up, 
subjects will continue to be monitored for efficacy until confirmed PD, death, or withdrawal of consent. 
After confirmed PD, subjects will be followed for survival, subsequent anti-myeloma therapies, second 
primary malignancies (SPMs) for both Arms, and other delayed adverse events for Arm B every 16 weeks 
until the end of the study. All subjects who received cilta-cel will continue to be monitored for long-term 
safety under a separate study for up to 15 years after cilta-cel administration.
Subjects who are unable to receive PVd or DPd standard therapy for Arm A, or unable to be apheresed, or 
receive bridging therapy, conditioning regimen or cilta-cel infusion for Arm B, will be followed until 
confirmed PD, start of a new anti-myeloma therapy, withdrawal of consent, or end of the study whichever 
occurs first. After PD, subjects will be followed for survival status, subsequent anti-myeloma therapies, and 
SPMs until the end of the study. 
EVALUATIONS
For both Arm A and Arm B, disease status will be evaluated according to the International Myeloma 
Working Group (IMWG) consensus recommendations for MM. Minimal residual disease (MRD) will be 
monitored in subjects using Next Generation Sequencing on bone marrow aspirate DNA.
Subjects randomized to Arm B will have blood and serum samples collected for assessment of cilta-cel
pharmacokinetics, immunogenicity, and biomarkers.
Data regarding subjects’ health-related quality of life, will be captured using patient-reported outcome 
measures in both Arm A and Arm B. Medical resource utilization data, associated with medical encounters, 
will also be collected for both treatment arms.
Safety evaluations will include a review of adverse events, laboratory test results, vital sign measurements, 
physical examination findings (including neurological examination), and assessments of cardiac function,
Immune Effector Cell-associated Encephalopathy (only for Arm B), and Eastern Cooperative Oncology 
Group performance status. 
Safety and efficacy data will be periodically reviewed by an Independent Data Monitoring Committee.
STATISTICAL METHODS
The sample size calculation is performed based on the assumption that cilta-cel can reduce the risk of PD
or death by 35%, ie, hazard ratio (cilta-cel vs. standard therapy) of 0.65, which translates into a median PFS 
of 20 months for the cilta-cel group, assuming the median PFS for the standard therapy arm is 13 months. 
Approximately 400 (200/treatment arm) subjects will be randomized to observe a total of 250 PFS events 
to achieve approximately 90% power to detect this hazard ratio with a log-rank test (2-sided alpha of 0.05). 
The sample size calculation has taken into consideration an estimated annual dropout rate of 5% and one 
interim analysis for efficacy.

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Status: Approved,  Date: 18 August 2022
o
Delayed AEs will be collected regardless of causality from the time of JNJ-68284528 administration (with the exception of SPMs, which are collected from the time of randomization) until the 
end of study, and subsequently in a separate long-term follow-up study for up to 15 years after last administration of JNJ-68284528. For subjects diagnosed with second primary malignancy, a 
tumor sample should be collected, and DNA, RNA, or protein analysis may be performed to investigate the presence of lentiviral elements
p
Delayed AEs include new malignancies or recurrence of pre-existing malignancy (all grades), new incidence or exacerbation of pre-existing neurologic disorder (all grades), new incidence or 
exacerbation of a pre-existing rheumatologic or other autoimmune disorder (all grades), new incidence of Grade ≥ 3 hematologic disorder, and new incidence of Grade ≥ 3 infections.
q
r
For additional information, refer to Section 8.3.1.
CD4/CD8 panel should be done for newly enrolled subjects. Subjects enrolled under amendment #1 that have re-consented to amendment #2 and have received cilta-cel are not required to do 
the CD4/CD8 lymphocyte panel.

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2.
INTRODUCTION
JNJ-68284528 (ciltacabtagene autoleucel [cilta-cel]) is an autologous chimeric antigen receptor 
T cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA), a molecule expressed on 
the surface of mature B lymphocytes and malignant plasma cells. Results from the Phase 1b 
portion of Study 68284528MMY2001 indicate that JNJ-68284528 has anti-myeloma activity and 
a safety profile consistent with the known mechanism of action of the product.
For the most comprehensive nonclinical and clinical information regarding JNJ-68284528, refer 
to the latest version of the Investigator's Brochure for JNJ-68284528.
The term "sponsor" used throughout this document refers to the entities listed in the Contact 
Information page(s), which will be provided as a separate document.
2.1.
Study Rationale
B-cell maturation antigen (BCMA) is a cell surface antigen highly expressed on cells of the B-cell
lineage. Comparative studies show a lack of BCMA in most normal tissues and absence of 
expression on CD34-positive hematopoietic stem cells. This selective expression and the 
biological importance for the proliferation and survival of myeloma cells makes BCMA a 
promising target for CAR-T based immunotherapy. Observed response rates and the reversible 
adverse events for most subjects, from the Legend-2 study and the ongoing the Phase 1b/2 
Study 68284528MMY2001, (described in detail in Section 2.2.5) support further investigation of 
this approach in the current study. As the degree of benefit of CAR-T therapy is dependent on a 
patient’s immune response, JNJ-68284528 could have potentially increased benefit, with greater 
durability of response when administered to patients with multiple myeloma (MM) who have less 
prior exposure to immunomodulatory and cytotoxic therapy. Fraietta initially demonstrated the 
prevalence of an early memory T-cell phenotype (CD27+ CD45RO- CD8+) in patients with 
chronic lymphocytic leukemia treated with CART19 was predictive of clinical response 
independent of other factors.15 The same finding has also been demonstrated with BCMA directed 
CAR-T.9 Furthermore, the same group has also shown that the early memory T-cell phenotype 
was significantly higher in newly diagnosed subjects post-induction chemotherapy as compared to 
relapsed-refractory subjects.10 Study 68284528MMY3002 aims to determine the safety and 
efficacy of JNJ-68284528 in myeloma subjects who have been less heavily pretreated than subjects 
on the Study 68284528MMY2001. For this current study subjects are required to have received 1 
to 3 prior line(s) of therapy, including prior exposure to a proteasome inhibitor (PI) and an 
immunomodulatory drug (IMiD), and who are refractory to lenalidomide.
Pomalidomide in combination with bortezomib and dexamethasone (PVd) and daratumumab in 
combination with pomalidomide and dexamethasone (DPd) were selected as the comparator 
regimens. Pomalidomide in combination with bortezomib and dexamethasone is approved in the 
European Union (EU) for subjects with MM, who have received at least 1 prior treatment regimen
including lenalidomide. While not approved in the United States (US), PVd is recommended 
(National Comprehensive Cancer Network Guidelines) for subjects with relapsed/refractory 
multiple myeloma (RRMM) who have received 2 or more prior lines of therapy including an IMiD 

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and a PI. Daratumumab in combination with pomalidomide and dexamethasone is approved in the 
US for the treatment of subjects with MM who have received at least 2 prior therapies including 
lenalidomide and a PI. While multiple newer treatment options have become available for subjects 
with relapsed myeloma, studies in lenalidomide refractory subjects show a progression-free 
survival (PFS) of only 8 to 11 months even in subjects with early relapse. Study 
68284528MMY3002 (CARTITUDE-4) was designed to improve outcomes in subjects with 
lenalidomide-refractory myeloma, by moving CAR-T therapy earlier in the treatment of relapsed 
myeloma and capitalizing on the less compromised immune system of subjects in early relapse. 
Given their proven efficacy and regulatory approvals, PVd and DPd will serve as comparators.
2.2.
Background
2.2.1.
Multiple Myeloma
Multiple myeloma is a malignant plasma cell disorder diagnosed annually in approximately 
86,000 patients worldwide.4 For patients with relapsed MM, the treatment is determined on an 
individual basis where the patient’s age, prior therapy, bone marrow function, co-morbidities, 
patient preference and time to relapse are considered. Common standard regimens include either 
a PI or an IMiD in combination with dexamethasone with or without a monoclonal antibody such 
as daratumumab. With each successive relapse, the depth and duration of response typically 
decreases. After relapse from PIs or IMiDs, patients are often retreated with drugs that have the 
same mechanism of action to which they have been sensitive. Often, the disease becomes 
refractory to all available therapies. Several studies have shown the poor prognosis of these 
subjects. For example, subjects refractory to both a PI and an IMiD have a median overall survival 
(OS) of only 8 to 9 months.21,44 For patients who are refractory to at least 3 prior lines of therapy, 
including PIs and IMiDs, the median OS decreases to only 5 months.44 Further, since it has become 
standard to use lenalidomide as a frontline regimen, most subjects with relapsed MM have disease 
that has become refractory to lenalidomide-based regimens.
2.2.2.
B-Cell Maturation Antigen
B-cell maturation antigen (BCMA, also known as CD269 and TNFRSF17) is a 20-kilodalton, 
type III membrane protein that is part of the tumor necrosis receptor superfamily.42 BCMA is 
predominantly expressed in B-lineage cells and plays a critical role in B cell maturation and 
subsequent differentiation into plasma cells.42 The expression characteristics of BCMA make it an 
ideal therapeutic target in the treatment of MM.16,42 BCMA binds 2 ligands that induce B-cell 
proliferation: a proliferation inducing ligand (APRIL; CD256) and B-cell activating factor (BAFF;
CD257).2,11,32 Upon binding of BCMA monomers to the APRIL trimer, activation and 
phosphorylation of p38MAPK, ELK, and NF-κB are triggered through intracellular tumor necrosis 
factor receptor-associated factor molecules leading to pro-survival gene regulation.5,18,20

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2.2.3.
CAR-T Therapy
Chimeric antigen receptor T (CAR-T) cell therapy uses modified autologous T cells that are 
activated in an MHC-independent manner upon binding to their target. This results in lysis of the 
targeted cells. Kymriah® (tisagenlecleucel) and Yescarta&
(axicabtagene ciloleucel), 
CD19-directed CAR-T based therapies, have been approved in the US for the treatment of patients 
with B-cell malignancy.23,45 An ongoing Phase 1 clinical study with bb2121 (NCT02658929), a 
BCMA-directed CAR-T immunotherapy, demonstrated promising results for this strategy in 
relapsed/refractory MM.38 Of the first 33 consecutive subjects to receive an infusion of bb2121,
76% experienced cytokine release syndrome (CRS), which was Grade 1 or 2 in 23 subjects (70%) 
and Grade 3 in 2 subjects (6%). Neurologic toxicity occurred in 42% of subjects. The objective 
response rate (partial response or better) was 85%, including 15 subjects (45%) with complete 
responses. A median PFS of 11.8 months was observed for the 30 subjects who received 
≥150 x 106 CAR-positive T-cells (for the most recent information, refer to the ABECMA USPI).1
The approval of Kymriah and Yescarta, together with preliminary study results with bb2121, 
suggest that administering BCMA-directed CAR-T immunotherapy may be an effective means to 
treat MM.
2.2.4.
JNJ-68284528
Results from the Phase 1b portion of Study 68284528MMY2001 indicate that JNJ-68284528 has 
significant anti-myeloma activity and a safety profile consistent with the known mechanism of 
action of the product. 
The LCAR-B38M coding sequence is comprised of a human CD8 alpha signal peptide (CD8α SP), 
BCMA targeting domain consisting of 2 different VHH (single domain antibody, clone VHH1 and 
VHH2), human CD8 alpha hinge and transmembrane domain (CD8α hinge+TM), human CD137 
cytoplasmic 
domain, 
and 
a 
human 
CD3 
zeta 
cytoplasmic 
domain 
(CD3ζ) 
(Figure 2). The expression of LCAR-B38M is driven and controlled by a human elongation 
factor 1 alpha promoter (hEF1α promoter).
Figure 2:
LCAR-B38M Coding Region
The JNJ-68284528 drug product used in this study and the LCAR-B38M CAR-T cell drug product 
used in the first-in-human Legend-2 study (See Section 2.2.5) express an identical CAR protein. 
The JNJ-68284528 drug product will be produced using a modified manufacturing and scale-up 
process. The LCAR-B38M CAR-T cell designation will be used when referring to results from the 
Legend-2 study. JNJ-68284528 will be used to reference the drug product in this study.
CD8∋SP
BCMA targeting domain
CD8∋hinge+ TM
CD137 cytoplasmic
hCD3 ( (cytoplasmic) 
VHH1
VHH2
GGGGS linker

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A summary of the in vitro and in vivo pharmacology, safety pharmacology, toxicology studies, 
and clinical studies with LCAR-B38M CAR-T cells are presented in the following sections. 
2.2.5.
Summary of Nonclinical and Clinical Studies
For the most comprehensive nonclinical and clinical information, refer to the latest version of the 
Investigator's Brochure.
Nonclinical Studies
The nonclinical pharmacology program was designed to characterize the biological activity and 
mechanism of action of LCAR-B38M CAR-T cells. In vitro mechanistic proof-of-principle studies 
have assessed target engagement with respect to:
!
On-target binding (ie, binding of VHH to BCMA),
!
Off-tumor target activity (ie, in human non-myeloma cell lines, including lung, liver, breast, 
brain, embryonic kidney and kidney expressing hERG),
!
On-tumor target activity (ie, in human MM cell lines),
In vivo studies have evaluated the safety and efficacy of LCAR-B38M CAR-T cells.
The nonclinical studies support JNJ-68284528 as an effective targeted therapy against 
BCMA-expressing MM. Refer to the Investigator’s Brochure for a complete description of the 
nonclinical study information.
Clinical Studies
Legend-2
Legend-2 is a first-in-human, single-arm, open-label, multicenter study to determine the safety and 
efficacy of LCAR-B38M CAR-T cells used to treat subjects with relapsed or refractory MM. Study 
enrollment was completed in November 2017; 74 subjects have been treated on this study. The 
clinical cutoff for the analysis presented here was 06 February 2018, with updated survival, 
efficacy data, and CRS grading provided as of 31 December 2018. As of the 31 December 2018 
update, the median follow-up was 17.41 months (range: 0.4–32.2 months).
All subjects had relapsed or refractory MM with a median of 3 (range: 1-9) prior lines of therapy 
including PI therapy (73%), IMiD (87.8%), and both PI and IMiD (64.9%). Prior autologous stem 
cell transplantation was reported for 24.3% of subjects. The median age at study entry was 
54.5 years (range: 27-74 years). 
Of the 74 subjects included in the Legend-2 study, 68 (91.9%) subjects had an adverse event of 
CRS (median time to onset 9 days [range: 3-57 days]). Most of the CRS events were Grade 1 or 
Grade 2 severity. Six (8.1%) subjects experienced Grade 3 CRS and 1 (1.4%) subject experienced 
Grade 5 CRS. The fatal event of CRS occurred in a subject who experienced CRS and tumor lysis 
syndrome and died on Day 13 after receiving the LCAR-B38M CAR-T cell infusion. For most
subjects, symptoms of CRS were mild and reversible. Grade 1 neurotoxicity was reported for 
1 subject.

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In addition to the subject who died from CRS, 1 subject had a fatal adverse event of potential acute 
pulmonary embolism and potential acute coronary syndrome related to treatment with 
LCAR-B38M CAR-T cells.
As of the 31 December 2018 update, the overall response rate (complete response [CR]+very good 
partial response [VGPR]+partial response [PR]) was 87.8%. Complete response was achieved by 
54 (73.0%) subjects and 49 (66.2%) subjects were negative for MRD as assessed by bone marrow 
8-color flow cytometry assay. The Kaplan-Meier estimate of median duration of response was 
22 months (95% confidence interval [CI]: 11.79-29.14). The median PFS for the overall 
population was 16 months (95% CI: 10.61-28.16) and among the 49 subjects achieving 
MRD-negative CR, the median duration of response was 28 months. For current information, refer 
to the latest version of the JNJ-68284528 Investigator's Brochure.
Study 68284528MMY2001
As of the 24 June 2019 data cutoff, 25 subjects had received an infusion of JNJ-68284528 in the 
Phase 1b portion of Study 68284528MMY2001. The safety profile is consistent with observations 
from the Legend-2 study. 
!
Twenty-four of the 25 subjects who received JNJ-68284528 had at least 1 treatment-emergent 
adverse event (TEAE). 
)
The most commonly reported TEAEs (>20% of subjects) were CRS (88.0%), neutropenia 
(80.0%), anemia (76.0%), thrombocytopenia (72.0%), leukopenia (40.0%), lymphopenia 
(28.0%), fatigue (24.0%), headache (24.0%), cough (24.0%), and diarrhea (20.0%)
!
Grade 3 or 4 TEAEs were reported for 24 of the 25 subjects. 
)
The most commonly reported Grade 3 or 4 TEAEs (>10% of subjects) were neutropenia 
(76.0%), anemia (48%), thrombocytopenia (60.0%), and leukopenia (40.0%), 
lymphopenia (16.0%) and CRS (16.0%). 
!
Serious adverse events were reported for 6 subjects: 
)
One subject had serious TEAEs of Grade 3 CAR-T cell-related encephalopathy syndrome 
(CRES) and Grade 3 CRS.
)
One subject had serious TEAEs of CRS, with Grade 5 hemophagocytic 
lymphohistiocytosis (HLH) secondary to CRS, and Grade 4 acute kidney injury.
)
One subject had serious TEAEs of Grade 4 thrombocytopenia and Grade 3 pneumonia.
)
One subject had a serious TEAE of Grade 2 mental status change.
)
One subject had a serious TEAE of Grade 3 encephalitis.
)
One subject had serious TEAEs of Grade 1 CRS and Grade 1 confusional state.
!
One subject died on Day 99 due to CRS, with Grade 5 HLH secondary to CRS. 
!
Twenty-two of the 25 subjects (88.0%) experienced CRS. Three subjects experienced Grade 3 
CRS and 1 subject experienced Grade 5 CRS (as noted above).

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!
CAR-T cell-related neurotoxicity was reported in 4 subjects. One subject had Grade 3 CRES, 
the second subject had Grade 1 neurologic adverse events (dysarthria, slow mentation, gait 
disturbance, and somnolence), the third subject had Grade 1 CRES, and the fourth subject had 
a Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) event (difficulty 
in finding words). All events occurred in the setting of CRS.
The median duration of follow-up for the 21 subjects who received JNJ-68284528 and had at least 
1 post-dose disease evaluation as of 24 June 2019 was 2.99 months (range: 1.3 to 9.9 months). 
Among these 21 subjects, 19 subjects achieved at least a partial response (PR) with an ORR (PR
or better) of 90.5% (including unconfirmed responses) with 13 subjects (61.9%) having VGPR or 
better and 6 subjects (28.6%) having CR or better. A stringent complete response (sCR) was 
achieved by 4 subjects. Fifteen subjects had post-baseline bone marrow samples available for 
MRD assessment. All 10 subjects (100%) evaluable at the 10-5 sensitivity level were negative for 
MRD by next generation flow cytometry and/or next generation sequencing (NGS; Adaptive v 
2.0). Two subjects were indeterminate at 10-5 due to insufficient cell counts but were MRD 
negative at the sensitivity threshold of 10-4 by NGS. No clone identification could be performed 
in 3 subjects by NGS. Follow-up for response continues, however these preliminary data suggest 
compelling efficacy in this population of heavily pre-treated subjects. For current information, 
refer to the latest version of the JNJ-68284528 Investigator's Brochure.
Other Neurotoxicities in Study 68284528MMY2001
CAR-T cell neurotoxicity is categorized as ICANS as well as other neurotoxicity determined by 
the investigator to be related to CAR-T therapy and occurring after recovery from CRS and/or 
ICANS. As of the 01 September 2020 clinical cutoff, 20
participants (20.6%) in 
Study 68284528MMY2001 experienced a treatment-emergent CAR-T cell neurotoxicity event.
All-grade ICANS were reported for 16 participants (16.5%). Of these, 2 participants (2.1%) 
developed maximum Grade 3 or 4 ICANS. Median time from cilta-cel infusion to ICANS onset 
was 8 days (range: 3 to 12 days), and the median duration of ICANS was 4 days (range: 1 to 12 
days). Fifteen participants experienced ICANS concurrent with CRS and 1 participant experienced 
ICANS 4 days after the recovery of CRS. 
Twelve participants (12.4%) experienced other CAR-T cell neurotoxicity not defined as ICANS 
as assessed by the Investigator either due to symptoms or time of onset (ie, occurring after period 
of recovery from CRS and/or ICANS). These events included a variety of symptoms with varying 
severity including disturbances in consciousness, coordination and balance, movement disorders, 
mental impairment, cranial nerve disorders, and peripheral neuropathies. 
Five of these 12 participants experienced a similar presentation of movement and neurocognitive 
TEAEs. These included a cluster of movement (eg, micrographia, tremors, etc), cognitive (eg, 
memory loss, disturbance in attention, etc) and personality change (eg, reduced facial expression, 
flat affect, etc) TEAEs that were observed to progress to an inability to work or care for oneself 
(disabling). This cluster of movement and neurocognitive TEAEs appears potentially to be 
associated with a combination of 2 or more factors such as higher tumor burden, prior Grade 2 or 
higher CRS, prior ICANS, and high CAR-T cell expansion and persistence.
The neurotoxicity was Grade 1 or 2 in 3 participants (3.1%), Grade 3 or 4 in 8 participants (8.2%) 
and Grade 5 in 1 participant (1.0%). These events had a median onset of 26.5 days from cilta-cel 

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infusion (range: 11 to 108 days) with a median duration of 74.5 days (range: 2 to 160 days). At the 
time of clinical data cutoff, 6 (50%) had resolved, 4 (33%) were ongoing at the time of death due 
to other causes, and 1 is ongoing in a participant still in follow-up; one case (8.3%) was fatal.
Study 68284528MMY2002
Study 68284528MMY2002 is a Phase 2, open-label, multicenter study in China (sponsored by 
Legend Biotech HK Limited and Janssen R&D; Investigational New Drug holder is Legend 
Biotech) to evaluate the efficacy and safety of LCAR-B38M CAR-T cells in adult subjects with 
relapsed or refractory MM. Approximately 60 subjects will be enrolled into the study. The primary 
objective is to evaluate the efficacy of LCAR-B38M CAR-T cells. 
The first subject was dosed on 22 March 2019. As of 9 Dec 2019, 25 subjects were enrolled into 
the study and 13 subjects received LCAR-B38M CAR-T cells. Of the 12 subjects analyzed in the 
second safety evaluation team meeting, 12 subjects were reported with CRS, 1 subject had 
Grade 1, 5 had Grade 2, 5 had Grade 3 and 1 had Grade 4 CRS. The median onset to CAR-T 
infusion was 7 days (range: 2-8) and median duration of CRS was 5 days (range: 4-8). One subject 
received an infusion of LCAR-B38M CAR-T cells on 06 May 2019 and died on 
2019 due 
to hemorrhage secondary to thrombocytopenia. The investigator attributed the thrombocytopenia, 
CRS, and acute renal failure to LCAR-B38M CAR-T cell therapy. The CRS events experienced 
by other subjects all resolved. No neurotoxicity has been reported as of the cut-off date. For current 
information, refer to the latest version of the JNJ-68284528 Investigator's Brochure.
Study 68284528MMY2003
Study 68284528MMY2003 is an ongoing, multicohort, open-label, multicenter, Phase 2 study to 
determine whether treatment with cilta-cel results in MRD negativity in adult participants with 
MM. Cohorts of approximately 20 to 40 participants each, representing unique populations of 
patients with MM of unmet medical need, are planned. As of 23 July 2020, 18 participants have 
received cilta-cel infusion. Further details are provided in the most recent edition of the
JNJ-68284528 Investigator’s Brochure.
2.2.6.
Comparator Agents
2.2.6.1.
Pomalidomide, Bortezomib, and Dexamethasone
Pomalidomide, bortezomib and low-dose dexamethasone combination was studied in the Phase 1
Study MM-005 in lenalidomide-refractory and PI-exposed relapsed or refractory MM subjects.39
Subjects received pomalidomide (1–4 mg on Days 1–14), bortezomib (1-1.3 mg/m2 on Days 1, 4, 
8, and 11 for Cycles 1–8; Days 1 and 8 for Cycle ∀9) as well as dexamethasone 20 mg given on 
Days 1, 2, 4, 5, 8, 9, 11 and 12 in 21-day cycles. Subjects (n=34) received a median of 2 prior lines 
of therapy. With no dose-limiting toxicities, maximum tolerated dose (MTD) was defined as the 
maximum planned dose: pomalidomide 4 mg, bortezomib 1.3 mg/m2. The most common Grade 3
or 4 TEAEs were neutropenia (44%) and thrombocytopenia (26%). ORR was 65% and the median 
duration of response was 7.4 months. 
PPD

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In the Phase 3 OPTIMISMM study,40 subjects with relapsed or refractory MM with 1 to 3 prior 
line(s) of therapy were randomized to either PVd (n=281) or bortezomib/dexamethasone (Vd) 
(n=278) on the same schedule and at the defined MTD as in the Study MM-005. Seventy percent 
of subjects were lenalidomide-refractory. Subjects had a median of 2 prior lines of therapy. The 
most common Grade 3 or 4 TEAEs were neutropenia (42%), thrombocytopenia (27%) in subjects
treated with PVd. In the same group, the most common Grade 3 or 4 non-hematologic toxicities 
were: infection (31%) with 12% of subjects having pneumonia. The febrile neutropenia rate was 
3% in the PVd group. Grade 3 or 4 peripheral sensory neuropathy was reported in 8% of subjects
receiving PVd. The ORR was 82 % and 50% in the PVd and Vd cohorts, respectively. VGPR or 
better was achieved by 53% and 18% of the subjects in the PVD and Vd cohorts, respectively. The 
median PFS in the entire population was 11.2 months on the PVd cohort versus 7.1 months on the 
Vd cohort. The median PFS was 9.5 months in lenalidomide-refractory subjects on the PVd cohort
versus 5.6 months on the Vd cohort. Lenalidomide-refractory subjects with only 1 prior line of 
therapy had a median PFS of 17.8 months on the PVd regimen versus 9.5 months on the Vd
regimen. Based on these results, PVd was approved in the EU for patients with relapsed or 
refractory MM and is National Comprehensive Cancer Network29 recommended in the US for 
patients whose MM has relapsed after 2 or more therapies including an IMiD and a PI and is 
therefore being used as a comparator for this current Phase 3 study. 
For further information regarding PVd refer to the current approved label for 
Pomalyst®/Imnovid®/pomalidomide (Pomalyst Prescribing Information; Imnovid Summary of 
product Characteristics)19,33.
2.2.6.2.
Daratumumab, Pomalidomide, and Dexamethasone
Daratumumab (DARZALEX®) in combination with pomalidomide and dexamethasone (DPd) has 
been approved in the US for the treatment of patients with MM who have received at least 2 prior 
therapies including lenalidomide and a proteasome inhibitor.  
The approval was based on data from the Phase I (EQUULEUS) study of DPd subjects with
relapsed or refractory MM. One arm of the EQUULEUS open-label study included 103 subjects
with MM who had received prior treatment with a PI and an IMiD. Subjects in the study received 
DPd. Subjects had a median of 4 prior lines of therapy and 89% were lenalidomide-refractory.
The ORR in the study was 59%, with 9% of subjects achieving a CR and 8% achieving a sCR. 
Median PFS was 8.8 months. Among the 62 responders, median duration of response was not 
estimable ([NE]; 95% CI: 13.6-NE).6 Based on these results, the DPd regimen was chosen as an 
alternative 
standard 
therapy
to 
be 
used 
as 
a 
comparator 
for
this 
current 
Study 68284528MMY3002. This regimen is also being explored in the context of an ongoing 
randomized open-label, active-control, multicenter Phase 3 study in subjects with relapsed or 
refractory multiple myeloma who had received at least 1 prior treatment regimen with both 
lenalidomide 
and 
a 
PI, 
and 
had 
demonstrated 
disease 
progression 
(APOLLO; 
EMN14/54767414MMY3013).
A total of 304 subjects were randomized (151 DPd; 153 Pd). Subjects had a median of 2 prior lines 
of therapy: 79.6% of subjects were refractory to lenalidomide, 48.0% were refractory to a PI, and 

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42.4% were refractory to both. The median duration of treatment was 11.5 months with DPd.
Results of the primary analysis demonstrated that the study met its primary endpoint of improved 
PFS, with a median PFS of 12.4 months, versus 6.9 months for subjects treated with Pd. With a 
median follow-up of 16.9 months, 99 subjects (33%) have died; the HR for OS was 0.91 (95% CI, 
0.61-1.35); survival data are immature and follow-up is ongoing. The ≥CR rates for D-Pd versus
Pd were 24.5% versus 3.9%; ≥VGPR rates were 51.0% vs 19.6%.
A formulation of daratumumab for subcutaneous (SC) administration was developed to shorten 
the time required to administer daratumumab and to lessen the rate and severity of infusion-related 
reactions (IRRs) observed with intravenous (IV) daratumumab. A recombinant human 
hyaluronidase PH20 (rHuPH20) was used to decrease the injection volume required, facilitating 
the subcutaneous administration of daratumumab.
The efficacy and adverse event profile of subcutaneous daratumumab are similar to those of IV 
daratumumab, with the exception of IRRs. Subcutaneous daratumumab has a lower rate of IRRs 
(16% versus 50% with IV administration). In addition, the IRRs mainly occur within 6 hours of 
the start of the first administration. The SC formulation of daratumumab is being evaluated in 
Study MMY1004, an open label, multicenter, dose escalation Phase 1b study to assess the safety, 
pharmacokinetics, and efficacy of subcutaneous daratumumab in participants with relapsed or 
refractory MM. The fixed SC dose of 1800 mg was selected based on a review of 
pharmacokinetics, safety, and efficacy data in Part 1 (N=53; daratumumab administered by 
subcutaneous infusion) and was confirmed in Part 2 (N=25; daratumumab administered by 
subcutaneous injection). Similar or greater maximum trough concentrations were observed 
following administration of SC daratumumab 1800 mg compared with standard approved dosing 
of IV daratumumab 16 mg/kg.41 The IRR rate in Part 2 was 16%; events were mostly Grade 1 or 
2 and included chills, dyspnea, sneezing and allergic rhinitis. Two Grade 3 events of reversible 
hypertension were reported. None of the IRRs led to treatment discontinuation. Injection-site 
reactions included reversible erythema in 24% of participants. Reversible induration at the 
injection site was experienced by 1 participant (4%). Subcutaneous daratumumab injections in the 
periumbilical area were well tolerated. The ORR in Part 2 was 52%, with 28% VGPRs and 4% 
CRs. Median time to response was 1 month. Median duration of response was 15.7 months and 
several responses deepened over time. The SC formulation currently is being tested in 
Study MMY3012, a Phase 3 study of IV daratumumab 16 mg/kg versus SC daratumumab 
1800 mg in participants with relapsed or refractory MM; and in Study MMY2040, a Phase 2 study 
of SC daratumumab in combination with standard MM treatment regimens. The randomized, 
open-label, non-inferiority, Phase 3 Study MMY3012 of SC daratumumab 1800 mg versus IV 
daratumumab 16 mg/kg in subjects with RRMM (n=263 SC; n=259 IV) confirmed non-inferiority 
for efficacy and pharmacokinetics, a similar adverse event profile, and a significantly reduced risk 
of IRRs (12.7% vs. 34.5%; P<0.0001) with daratumumab SC compared with daratumumab IV.26
For further information regarding DPd refer to the DARZALEX® local prescribing information or 
Summary of Product Characteristics (SmPC).12,13

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Randomization will be stratified by investigator’s choice of PVd or DPd, International Staging 
System (ISS) (I vs. II vs. III) (Section 10.5), and number of prior lines of therapy (1 vs. 2 or 3).
Data regarding subjects’ health-related quality of life (HRQoL), symptoms, functioning, and 
general well-being will be captured using patient reported outcomes (PRO) measures. Medical 
resource utilization data, associated with medical encounters, will also be collected.
4.1.1.
Arm A
Prior to screening, the investigator will determine if the subject will be treated with PVd or DPd, 
as standard therapy based on the subject’s prior exposure to anti-myeloma therapies. After meeting 
eligibility criteria defined in Section 5.1 and Section 5.2, subjects randomized to Arm A will 
receive either PVd or DPd. Subjects should start PVd or DPd within 7 days after randomization.
Pomalidomide, bortezomib and dexamethasone (PVd):
Pomalidomide will be administered at a full dose of 4 mg orally (PO) on Days 1 through 14 of 
each 21-day cycle.
Bortezomib will be administered at a full dose of 1.3 mg/m2 subcutaneously (SC) twice a week for 
2 weeks for the first 8 Cycles and then once a week for 2 weeks from Cycle 9 onwards of each 21-
day cycle. Bortezomib doses should always be administered at least 72 hours apart. 
Dexamethasone will be administered PO as 20 mg/day (≤75 years of age) or 10 mg/day (>75 years 
of age) on Days 1, 2, 4, 5, 8, 9, 11, and 12 from Cycles 1 through 8 and on Days 1, 2, 8 and 9 from 
Cycle 9 onwards for each 21-day cycle.
Daratumumab, pomalidomide and dexamethasone (DPd):
Daratumumab will be given at a dose of 1800 mg SC at weekly intervals for Cycles 1 and 2, then 
every 2 weeks for Cycles 3 to 6, then every 4 weeks from Cycle 7 onwards of each 28-day cycle. 
Subjects will receive pre-treatment medications to mitigate potential IRRs.
Pomalidomide will be administered at full dose of 4 mg PO on Days 1 through 21 of each 28-day 
cycle.
Dexamethasone will be administered PO/IV at a total dose of 40 mg weekly (20 mg weekly for 
subjects >75 years of age) of each 28-day cycle (see Section 6.1.1). 
Safety and efficacy will be assessed, and subjects randomized to Arm A will continue to receive 
PVd or DPd until confirmed progressive disease (PD), death, intolerable toxicity, withdrawal of 
consent, or end of the study. All subjects in Arm A will have an end-of-treatment visit. Subjects 
who discontinue PVd or DPd for any reason, other than PD or withdrawal of consent, will continue
to be followed for response assessment until confirmed PD or the start of a subsequent 
anti-myeloma therapy. After confirmed PD, subjects will then be followed for survival status, 
subsequent anti-myeloma therapies, response to subsequent anti-myeloma therapies including the
date of subsequent progression (PFS2), and the occurrence of second primary malignancies 
(SPMs) every 16 weeks until the end of the study (defined when approximately 250 deaths have 

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occurred). The occurrence of SPMs must be reported throughout study treatment and must 
continue to be reported until the end of the study.
4.1.2.
Arm B
Eligible subjects randomized to Arm B will receive JNJ-68284528 and will undergo the following 
steps:
!
Apheresis to collect peripheral blood mononuclear cells (PBMCs) Apheresis should be 
performed 3 to 6 days after randomization. 
!
Bridging therapy should be started after apheresis but no more than 7 days after 
randomization. Subjects should receive at least one cycle of bridging therapy with either PVd 
or DPd (determined by the investigator based on the subject’s prior anti-myeloma therapy). 
Additional cycles of bridging therapy may be considered based on subject’s clinical status and 
timing of availability of JNJ-68284528. Investigator must contact the sponsor for approval.
Cycles beyond Bridging Cycle 1 may be truncated to allow for adequate washout and 
minimize time off therapy.
!
A wash-out period must occur from the last dose of bridging therapy until prior to initiating 
the conditioning regimen, the length of which will depend on whether PVd or DPd was given 
as bridging therapy (See Section 6.1.5.4).
!
Conditioning regimen of IV cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily 
for 3 days. The dose of fludarabine should be reduced to 24 mg/m2 for subjects with an 
estimated glomerular filtration rate (eGFR) of 30 to 70 mL/min/1.73 m2.
!
JNJ-68284528 will be administered with the target dose of 0.75 x 106 CAR-positive viable 
T cells/kg 5 to 7 days after the start of the conditioning regimen. 
!
Post-infusion Follow Up: Intensive safety, pharmacokinetics (PK), biomarkers, and efficacy
monitoring during the first 112 days following JNJ-68284528 administration.
!
Post-treatment Follow Up: starts once the post-infusion follow-up is complete (on Day 112) 
and lasts until end of study. In the post treatment follow-up phase, subjects will continue to 
be monitored for efficacy until confirmed PD, death, or withdrawal of consent. After 
confirmed PD, subjects will be followed for survival, subsequent anti-myeloma therapies, 
response to subsequent anti-myeloma therapies, including the date of subsequent progression 
(PFS2), and delayed AEs (including SPMs) every 16 weeks until the end of the study (defined 
when approximately 250 deaths have occurred).
The occurrence of delayed AEs including SPMs must be reported during the post-infusion and 
post-treatment follow-up phases and continue until the end of the study. All subjects who received 
JNJ-68284528 will continue to be monitored for long-term safety under a separate study for up to 
15 years after JNJ-68284528 administration.
Subjects in Arm B for whom apheresis or manufacturing fails may be allowed additional attempts 
at apheresis or manufacturing and may be allowed additional bridging therapy following 
discussion with the sponsor.

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Efficacy and safety evaluation (Arm A and Arm B)
For both Arm A and Arm B, disease status will be evaluated according to the IMWG consensus 
recommendations for MM treatment response criteria (Section 10.7).14,22,36 The primary endpoint
and response-related secondary endpoints will be determined using a validated computer 
algorithm.
Safety evaluations will include a review of adverse events, laboratory test results, vital sign 
measurements, physical examination findings, (including neurological examination), assessments 
of cardiac function, Immune-effector Cell-associated Encephalopathy (ICE) assessment (only for 
Arm B), and handwriting assessments (only for Arm B), and Eastern Cooperative Oncology Group
(ECOG) performance status.
Subjects who are unable to receive PVd or DPd standard therapy (Arm A), or unable to be 
apheresed, or receive bridging therapy, conditioning regimen or JNJ-68284528 infusion (Arm B) 
will be followed until confirmed PD, start of a new anti-myeloma therapy, withdrawal of consent,
or end of study, whichever occurs first. Once PD is confirmed, subsequent disease assessments 
time points are not required. After PD subjects will then be followed for survival status, subsequent 
anti-myeloma therapies, response to subsequent anti-myeloma therapies including the date of 
subsequent progression (PFS2), and SPMs until the end of the study (see Section 8.3). Subjects 
who progress on Arm B prior to receiving JNJ-68284528 and who are intended to get 
JNJ-68284528 as part of their subsequent therapy will continue to be monitored for response 
evaluation via central laboratory if feasible and safety monitoring as per Table 5 (refer to 
Section 1.3).
One interim analysis for efficacy is planned for PFS. The interim analysis will be performed when 
approximately 188 PFS events, which is 75% of the total planned PFS events, are observed. The 
final analysis of PFS will be performed after approximately 250 PFS events are observed. The end 
of the study is defined as the time when approximately 250 deaths have occurred or the sponsor 
terminates the study, whichever occurs first.
After the end of the study, the sponsor will continue to monitor subjects treated with JNJ-68284528 
for up to 15 years after administration of JNJ-68284528 on a separate long-term follow-up study 
(Study 68284528MMY4002) for complications of lentiviral integration, potential delayed adverse 
events, including SPMs.
All study evaluations will be conducted according to the Schedule of Activities (Section 1.3). A 
diagram of the study design is provided in Section 1.2, Schema.
Safety and efficacy data will be periodically reviewed by an Independent Data Monitoring 
Committee (Section 9.6 and Section 10.3).

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4.2.
Scientific Rationale for Study Design
Control, Study Phase/Periods, Intervention Groups
Randomization will be used to minimize bias in the assignment of subjects to intervention groups, 
to increase the likelihood that known and unknown subject attributes (eg, demographic and 
baseline characteristics) are evenly balanced across intervention groups, and to enhance the 
validity of statistical comparisons across intervention groups. Randomization will be stratified by 
investigator’s choice of PVd vs. DPd, ISS at screening (I vs. II vs. III), and number of prior lines 
of therapy (1 vs. 2 or 3).
Rationale for Pharmacokinetics (PK) and Immunogenicity Assessments
Data obtained from the JNJ-68284528 Treatment Arm (Arm B) in this study will provide 
information about the PK profile of JNJ-68284528 in subjects with MM. Therefore, samples will 
be obtained from all subjects in Arm B for PK assessments. Data may also be used for a population 
PK analysis to estimate additional PK parameters and provide information about the determinants 
of inter-subject variability in this population.
Immunogenicity to JNJ-68284528 is possible. Therefore, the presence of anti-JNJ-68284528
antibodies will be determined from PK samples collected from all subjects in the JNJ-68284528 
Treatment Arm (Arm B).
Rationale for DNA and Biomarker Collection
Biomarker samples will be collected to evaluate the depth and durability of clinical response 
through evaluation of MRD, using DNA sequencing of immunoglobulin genes. 
Rationale for Patient-reported Outcome Evaluations
Patient-reported outcome (PRO) data complements clinical and laboratory findings to describe the 
subject experience, directly reported by the subject. In addition, PRO data captures inputs required 
for cost-effectiveness modeling and helps to communicate the value of treatment to patients, 
clinicians, regulators, and payers.
4.2.1.
Study-Specific Ethical Design Considerations
This study is designed to provide an efficacious regimen for the treatment of subjects with 
lenalidomide-refractory MM. Based on the data presented in Section 2.2.4, treatment with 
JNJ-68284528 is anticipated to provide benefit to subjects in this study. Potential safety risks and 
mitigation strategies are outlined in Section 2.3. Subjects will be closely monitored. 
Potential subjects will be fully informed of the risks and requirements of the study and, during the 
study, subjects will be given any new information that may affect their decision to continue 
participation. They will be told that their consent to participate in the study is voluntary and may 
be withdrawn at any time with no reason given and without penalty or loss of benefits to which 
they would otherwise be entitled. Only subjects who are fully able to understand the risks, benefits, 
and potential adverse events of the study, and provide their consent voluntarily will be enrolled.

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The primary ethical concern is clinical equipoise among treatment groups. Both PVd and DPd 
have demonstrated durable responses in patients with MM who are refractory to lenalidomide. 
Based on the results of the OPTIMISMM study, in subjects with a median of 2 prior lines of 
therapy, PVd resulted in a median PFS of 11.2 months.40
The median PFS in 
lenalidomide-refractory subjects was 9.5 months. Subjects on the EQUULEUS study had a median 
of 4 prior lines of therapy and treatment with DPd resulted in a median PFS of 8.8 months.6 Results 
from the APOLLO study showed that in subjects with a median of 2 prior lines of therapy, 
treatment with DPd resulted in a median PFS of 12.4 months, versus 6.9 months for subjects treated 
with Pd. Experience with JNJ-68284528 in Study 68284528MMY2001 and LCAR-B38M CAR-
T cells in the Legend-2 study has shown ORRs of 90.5% and 87.8%, respectively (see Section 2.2.5). 
While one subject died in Study 68284528MMY2002 and one in Study 68284528MMY2001, both 
deaths were in the setting of rapid disease progression with numerous other factors likely 
contributing. To mitigate this, all subjects in Study 68284528MMY3002 will receive bridging 
therapy that is expected, in most cases, to control the subject’s myeloma while JNJ-68284528 
product is being manufactured. In addition, subjects with rapidly progressing disease or ≥Grade 3
thrombocytopenia or active infection will not be allowed to proceed to conditioning regimen on 
this study.
Use of JNJ-68284528 is hypothesized to result in greater response rates and duration of response 
when used in earlier lines of therapy due to improved immune function. This study will enroll 
subjects who have received 1 to 3 prior lines of therapy, that includes a PI and an IMiD, and who 
are refractory to lenalidomide. Based on nonclinical and clinical data, JNJ-68284528 is believed to 
be a reasonable treatment alternative for PVd and DPd regimens.
The blood volume to be collected is an acceptable amount of blood to be collected over this time 
period from the population in this study based upon the standard of the American Red Cross
(Section 8).
4.3.
Justification for Dose
4.3.1.
Rationale for PVd Dose Selection
The dose and schedule of PVd administration were selected based on the MM-005 and 
OPTIMISMM studies described in Section 2.2.6.1. The MTD defined in MM-005 and tested in 
the OPTIMISMM study is the dosing recommended by the Imnovid SmPC19 and will be used for 
the current study (68284528MMY3002).
4.3.2.
Rationale for DPd Dose Selection
The DPd dose selected for this study is based on the currently approved regimen of daratumumab 
in combination with pomalidomide and dexamethasone for the treatment of patients with MM who 
have received at least 2 prior therapies including lenalidomide and a PI. The SC formulation of 
daratumumab will be administered in this study, based on results from the COLUMBA study 
indicating a significantly lower rate of IRR with daratumumab SC compared with daratumumab 
IV.26

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4.3.3.
Rationale for JNJ-68284528 Dose Selection
The conditioning regimen of cyclophosphamide and fludarabine will lead to lymphodepletion and 
help promote CAR-T cell expansion in the subject. Cyclophosphamide and fludarabine before 
JNJ-68284528 infusion (Day 1) is consistent with the conditioning regimen used in the marketed 
CAR-T products.23,45
JNJ-68284528 will be administered at a targeted infused dose of 0.75 x 106 CAR-positive viable 
T cells/kg. This dose was established in the Phase 1b part of Study 68284528MMY2001. As of 
the 24 June 2019 data cutoff, 25 subjects have been infused with JNJ-68284528 in 
Study 68284528MMY2001; 21 subjects were evaluable for response (postbaseline evaluation at 
Day 28) with a median follow-up of 3 months (range 1–10). An ORR of 90.5% was observed with 
6 subjects achieving CR/sCR (28.6%), 7 subjects achieving VGPR (33.3%) and 6 subjects 
achieving PR (28.6%). The responses occurred rapidly, with most subjects exhibiting 
≥50% myeloma protein reduction at the first disease assessment (scheduled at Day 28 after 
JNJ-68284528 dosing). The responses continue to deepen for all subjects who are in follow up and 
no disease progression has been observed as of data cutoff.
Preliminary efficacy
data from Study 68284528MMY2001
showed that a dose of 
0.75 x 106 cells/kg of JNJ-68284528 CAR-T cell is highly efficacious with acceptable safety in a 
patient population who had no alternative treatment option. Further discussion of the
JNJ-68284528 dose selection is provided in the Investigator's Brochure.
4.4.
End of Study Definition
End of Study Definition
The end of study is when approximately 250 deaths have occurred in the study.
Study Completion Definition
A subject will be considered to have completed the study if he or she has either died before the 
end of the study, is not lost to follow-up, has not withdrawn consent for study participation or 
study terminated by sponsor. All subjects who received JNJ-68284528 will be offered to 
participate in a long-term follow-up study (Study 68284528MMY4002). The sponsor will 
continue to monitor consented subjects in the long-term follow-up study at least once per year for 
15 years. An appropriate transition will be arranged between this study and the long-term follow-
up study to ensure no follow-up gap occurs.
5.
STUDY POPULATION
Screening for eligible subjects will be performed within 28 days before randomization. Refer to 
Section 5.4, Screen Failures for conditions under which the repeat of any screening procedures is
allowed.
The inclusion and exclusion criteria for enrolling subjects in this study are described below. If 
there is a question about these criteria, the investigator must consult with the appropriate sponsor 

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representative and resolve any issues before enrolling a subject in the study. Waivers are not 
allowed. 
5.1.
Inclusion Criteria
Each potential subject must satisfy all the following criteria to be enrolled in the study:
1.
Be at least 18 years of age.
2.
Criterion modified per Amendment 2
2.1 Have documented diagnosis of MM as defined by the criteria below:
!
Multiple myeloma diagnosis according to the IMWG diagnostic criteria 
(Section 10.8).  
!
Measurable disease at screening as defined by any of the following:
)
Serum monoclonal paraprotein (M-protein) level ∀0.5 g/dL or urine M-protein 
level ∀200 mg/24 hours; or
)
Light chain MM without measurable M-protein in the serum or the urine: 
Serum free light chain ∀10 mg/dL and abnormal serum free light chain ratio.
Note: Local laboratory assessments may be used to establish measurable disease at 
Screening, with local laboratory result ≥125% of requirements. However, subjects
must have laboratory studies for diseases assessment received by central laboratory 
prior to randomization. If central and local laboratory studies are performed on the 
same day, only the central laboratory results will be considered.
3.
Have received 1 to 3 prior lines of therapy including a PI and IMiD. Subject must have 
undergone at least 1 complete cycle of treatment for each line of therapy, unless PD was 
the best response to the line of therapy (see Section 10.9). 
Note: induction with or without hematopoietic stem cell transplant, consolidation and
maintenance therapy is considered a single line of therapy.
4.
Have documented evidence of PD by IMWG criteria based on investigator’s 
determination on or within 6 months of their last regimen.
5.
Subjects with only 1 prior line of therapy must have progressed within 36 months of a 
stem cell transplant, or if not transplanted, then within 42 months of starting initial 
therapy.
6.
Criterion modified per Amendment 1
6.1. Criterion modified per Amendment 2
6.2. Be refractory to lenalidomide per IMWG consensus guidelines (Rajkumar 2011)36
(failure to achieve minimal response or progression on or within 60 days of completing 
lenalidomide therapy). Progression on or within 60 days of the last dose of lenalidomide 
given as maintenance will meet this criterion. For subjects with more than 1 prior line 

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of therapy, there is no requirement to be lenalidomide refractory to the most recent line 
of prior therapy. However, subjects must be refractory to lenalidomide in at least one 
prior line.
7.
Have an ECOG Performance Status score of 0 or 1 (Section 10.10).
8.
Have clinical laboratory values meeting the following criteria during the Screening 
Phase (re-testing is allowed but the below criteria must be met in the latest test prior to 
randomization):
!
Hemoglobin ≥8 g/dL (without prior RBC transfusion within 7 days before the 
laboratory test; recombinant human erythropoietin use is permitted);
!
Absolute neutrophil count (ANC) ≥1 × 109/L (without recombinant human 
granulocyte colony-stimulating factor [G-CSF] within 7 days and without 
pegylated G-CSF within 14 days of the laboratory test);
!
Platelet count ≥75 × 109/L (without prior platelet transfusion within 7 days before 
the laboratory test) in subjects in whom <50% of bone marrow nucleated cells are 
plasma cells; platelet count ≥50 x 109/L (without prior platelet transfusion within 
7 days before the laboratory test) in subjects in whom ≥50% of bone marrow 
nucleated cells are plasma cells;
!
Lymphocyte count ≥0.3 × 109/L;
!
Aspartate aminotransferase (AST) #3 × upper limit of normal (ULN);
!
Alanine aminotransferase (ALT) #3 × ULN;
!
Total bilirubin #2.0 × ULN; except in subjects with congenital bilirubinemia, such 
as Gilbert syndrome (in which case direct bilirubin #1.5 × ULN is required); 
!
Estimated glomerular filtration rate ∀40 mL/min per 1.73 m2 (to be calculated 
using the Modification of Diet in Renal Disease (MDRD) formula, (Section 10.11).
9.
Women of childbearing potential must have 2 negative pregnancy tests prior to starting 
PVd or DPd. The first, 10-14 days prior to the start of PVd or DPd and prior to 
randomization. The second pregnancy test will need to be done within 24 hours prior to 
the start of PVd or DPd. The investigator must verify that the results of these tests are 
negative prior to starting PVd or DPd. See Section 10.12 for definition of females who 
are not of reproductive potential.
10.
When a woman is of childbearing potential, the subject must commit either to abstaining
continuously from heterosexual intercourse or agree to use 2 methods of reliable birth 
control simultaneously. One of them a highly effective method of contraception (failure 
rate of <1% per year when used consistently and correctly; see examples below) and 
one other effective method (ie, male latex or synthetic condom, diaphragm, or cervical 
cap) and agree to remain on both methods from the time of signing the ICF until at least 
3 months after receiving the last dose of daratumumab or bortezomib or 28 days after 
the last dose of pomalidomide, whichever is later (Arm A) or at least 1 year after 
receiving a JNJ-68284528 infusion or at least 3 months after receiving the last dose of 

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daratumumab or bortezomib or 28 days after the last dose of pomalidomide, whichever 
is later (Arm B) (Section 10.12). Reliable contraception is indicated even where there 
has been a history of infertility, unless due to hysterectomy. Women of childbearing 
potential should be referred to a qualified provider of contraceptive methods, if needed.
Examples of highly effective contraceptives include:
!
User-independent 
methods: 
1) 
implantable 
progestogen-only 
hormone 
contraception associated with inhibition of ovulation; 2) intrauterine device; 
intrauterine hormone-releasing system; 3) vasectomized partner (vasectomy must 
be confirmed by 2 negative semen analyses);
!
User-dependent method: progestogen-only hormone contraception associated with 
inhibition of ovulation (oral or injectable). Estrogen-containing hormonal 
contraception is contraindicated due to increased risk of thromboembolic events 
with pomalidomide. Note: Hormonal contraception may be susceptible to 
interaction with the study treatment, which may reduce the efficacy of the 
contraceptive method. Refer to Section 10.12 for further information.
!
Women of childbearing potential must follow the contraception criteria outlined in 
the local pomalidomide pregnancy prevention program.
11.
A man must commit either to abstaining continuously from heterosexual sexual 
intercourse or a man:
!
Who is sexually active with a woman of childbearing potential or a pregnant 
woman  must agree to use a barrier method of contraception (eg, latex or synthetic 
condom with spermicidal foam/gel/film/cream/suppository) from the time of 
signing the ICF until at least 3 months after receiving the last dose of daratumumab 
or bortezomib or 28 days after the last dose of pomalidomide, whichever is later 
(Arm A) or at least 1 year after receiving a JNJ-68284528 infusion or at least 
3 months after receiving the last dose of daratumumab or bortezomib or 28 days 
after the last dose of pomalidomide, whichever is later (Arm B), even if they have 
undergone a successful vasectomy;
!
Should agree to practice contraception according to and for the time frame specified 
in the local pomalidomide pregnancy prevention program.
12.
Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, 
during the study and for at least 3 months after receiving the last dose of daratumumab 
or bortezomib, or 28 days after the last dose of pomalidomide, whichever is later 
(Arm A) or at least 1 year after receiving a JNJ-68284528 infusion or at least 3 months 
after receiving the last dose of daratumumab or bortezomib or 28 days after the last dose 
of pomalidomide, whichever is later (Arm B).
13.
Must sign an informed consent form (ICF) (or their legally acceptable representative 
must sign) indicating that he or she understands the purpose of, and procedures required 
for, the study and is willing to participate in the study. Subjects must be willing and able 

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to adhere to the prohibitions and restrictions specified in this protocol, as referenced in 
the ICF.
14.
Willing and able to adhere to the lifestyle restrictions specified in this protocol 
(Section 5.3)
5.2.
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study. The subject will be excluded if he or she has or had:
1.
Prior treatment with CAR-T therapy directed at any target.
2.
Any previous therapy that is targeted to BCMA.
3.
Ongoing toxicity from previous anticancer therapy that has not resolved to baseline 
levels or to Grade 1 or less; except for alopecia. 
4.
Subjects with Grade 1 peripheral neuropathy with pain or Grade 2 or higher peripheral 
neuropathy will not be permitted to receive PVd as standard therapy or bridging 
therapy; however, subject may receive DPd as standard therapy or bridging therapy.
5.
Received a cumulative dose of corticosteroids equivalent to ≥70 mg of prednisone 
within the 7 days prior to randomization (Section 10.13). 
6.
Criterion modified per Amendment 2
6.1. Was vaccinated with live attenuated vaccines within 6 weeks prior to 
randomization
7.
Subject received any antitumor therapy as follows, prior to randomization: 
!
Targeted therapy, epigenetic therapy, or treatment with an investigational drug or 
used an invasive investigational medical device within 14 days or at least 
5 half-lives, whichever is less;
!
Investigational vaccine within 4 weeks;
!
Monoclonal antibody treatment within 21 days;
!
Cytotoxic therapy within 14 days;
!
Proteasome inhibitor therapy within 14 days;
!
Immunomodulatory agent therapy within 7 days;
!
Radiotherapy within 14 days. However, if the radiation is given for palliative 
purposes and the radiation portal covered #5% of the bone marrow reserve, the 
subject is eligible irrespective of the end date of radiotherapy. Radiotherapy within 

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14 days on measurable extramedullary plasmacytoma(s) is not permitted even in 
the setting of palliation for symptomatic management.
8.
Active malignancies (ie, progressing or requiring treatment change in the last 
24 months) other than the disease being treated under study. The only allowed
exceptions are: 
!
non-muscle invasive bladder cancer treated within the last 24 months that is 
considered completely cured.
!
skin cancer (non-melanoma or melanoma) treated within the last 24 months that is 
considered completely cured.
!
non-invasive cervical cancer treated within the last 24 months that is considered 
completely cured.
!
localized prostate cancer (N0M0):
)
with a Gleason score of ≤6, treated within the last 24 months or untreated and 
under surveillance,
)
with a Gleason score of 3+4 that has been treated more than 6 months prior to 
full study screening and considered to have a very low risk of recurrence, or
)
history of localized prostate cancer and receiving androgen deprivation 
therapy and considered to have a very low risk of recurrence. 
!
Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in 
situ, or history of localized breast cancer and receiving antihormonal agents and 
considered to have a very low risk of recurrence.
!
Malignancy that is considered cured with minimal risk of recurrence.
  9.
Plasma cell leukemia at the time of screening, Waldenström’s macroglobulinemia, 
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal 
protein, and skin changes), or primary AL amyloidosis.
10.
Criterion modified in Amendment 1
10.1. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to 
JNJ-68284528 or its excipients, including dimethyl sulfoxide (refer to Investigator’s 
Brochure), or to fludarabine, cyclophosphamide, tocilizumab, pomalidomide, 
dexamethasone.
!
Subjects with contraindications or life-threatening allergies, hypersensitivity, or 
intolerance to daratumumab will not be permitted to receive DPd as standard 
therapy or bridging therapy; however, subjects may receive PVd as standard 
therapy or bridging therapy. Likewise, subjects with contraindications or life-
threatening allergies, hypersensitivity, or intolerance to bortezomib will not be 
permitted to receive PVd as standard therapy or bridging therapy; but may receive 
DPd as standard therapy or bridging therapy.

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11.
Pregnant or breast-feeding or planning to become pregnant while enrolled in this study 
or within 3 months of receiving the last dose of daratumumab or bortezomib, or within 
28 days after the last dose of pomalidomide, whichever is later (Arm A) or at least 
within 1 year after receiving JNJ-68284528 infusion or at least within 3 months after 
receiving the last dose of daratumumab or bortezomib or within 28 days after the last 
dose of pomalidomide, whichever is later (Arm B).
12.
Plans to father a child while enrolled in this study or within 3 months of receiving the 
last dose daratumumab or bortezomib, or within 28 days after the last dose of 
pomalidomide, whichever is later (Arm A) or at least within 1 year after receiving
JNJ-68284528 infusion or at least within 3 months after receiving the last dose of 
daratumumab or bortezomib or within 28 days after the last dose of pomalidomide, 
whichever is later (Arm B). 
13.
Stroke or seizure within 6 months of signing ICF.
14.
Received either of the following:
!
An allogenic stem cell transplant within 6 months before apheresis. Subjects who 
received an allogeneic transplant must have stopped all immunosuppressive 
medications for 6 weeks without signs of graft-versus-host disease. Subjects with 
active graft-versus-host disease are excluded.
!
An autologous stem cell transplantation #12 weeks before apheresis.
15.
Known active, or prior history of central nervous system (CNS) involvement or 
exhibits clinical signs of meningeal involvement of MM.
16.
Subject with chronic obstructive pulmonary disease (COPD) with a forced expiratory 
volume in 1 second (FEV1) <50% of predicted normal will not be able to receive DPd 
as standard therapy or bridging therapy; however, subject may receive PVd as standard 
therapy or bridging therapy. Note that FEV1 testing is required for subjects who are 
planned to receive treatment with DPd and are suspected of having COPD. 
17.
Criterion revised per Amendment 1
17.1. Any of the following:
a) Seropositive for human immunodeficiency virus (HIV)
b) Hepatitis B infection: In the event the infection status is unclear, quantitative 
viral levels are necessary to determine the infection status. Subjects who are 
anti-HBs positive and without history of vaccination or for subjects who are 
anti-HBc positive with or without positive anti-HBs should have hepatitis B 
virus (HBV)-DNA quantification test done. Please consult Section 10.6 for 
further details.

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c) Hepatitis C infection (defined as anti-hepatitis C virus [HCV] antibody positive 
or HCV-RNA positive) or known to have a history of hepatitis C. For subjects 
with known history of HCV infection, confirmation of sustained virologic 
response is required for study eligibility, defined as ≥24 weeks after completion 
of antiviral therapy.
18.
Criterion revised per Amendment 1
18.1. Criterion modified per Amendment 2
18.2. Serious underlying medical or psychiatric condition or disease, that is likely to 
interfere with study procedures or results, or that in the opinion of the investigator 
would constitute a hazard for participating in this study, such as:
!
Requirement of supplemental oxygen to maintain oxygen saturation;
!
Evidence of serious active viral or bacterial infection, requiring systemic 
antimicrobial therapy, or uncontrolled systemic fungal infection;
!
Active autoimmune disease;
!
Clinical evidence of dementia or altered mental status;
!
Any history of Parkinson’s disease or other neurodegenerative disorder
!
Clinically significant cardiac disease, such as:
)
New York Heart Association Class III or IV congestive heart failure (see 
Section 10.14);
)
Myocardial infarction or coronary-artery-bypass graft #6 months prior to 
enrollment;
)
History of clinically significant ventricular arrhythmia or unexplained 
syncope, not believed to be vasovagal in nature or due to dehydration;
)
History of severe non-ischemic cardiomyopathy;
)
Impaired cardiac function (LVEF <45%) as assessed by echocardiogram or 
multiple-gated acquisition (MUGA) scan performed #8 weeks before 
randomization.
19.
Major surgery within 2 weeks before randomization, or has not fully recovered from 
an earlier surgery, or has major surgery planned during the time the subject is expected 
to participate in the study. 
Note: Kyphoplasty or vertebroplasty are not considered major surgery. If there is a 
question about whether a procedure is considered a major surgery, the investigator 
must consult with the sponsor and resolve any issues before enrolling a subject in the 
study.
20.
Any issue that would impair the ability of the subject to receive or tolerate the planned 
treatment at the investigational site, to understand informed consent or any condition 
for which, in the opinion of the investigator, participation would not be in the best 

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interest of the subject (eg, compromise the well-being) or that could prevent, limit, or 
confound the protocol-specified assessments.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening
and before randomization. If a subject's clinical status changes (including any available laboratory 
results or receipt of additional medical records) after screening but before randomization such that 
he or she no longer meets all eligibility criteria, then the subject should be excluded from 
participation in the study. 
Section 5.4 (Screen Failures) describes options for retesting. The required source documentation 
to support meeting the enrollment criteria is noted in Section 10.3 - Regulatory, Ethical, and Study 
Oversight Considerations.
5.3.
Lifestyle Considerations
Potential subjects must be willing and able to adhere to the following lifestyle restrictions during 
the study to be eligible for participation:
1.
Refer to Section 6.5, Concomitant Therapy for details regarding prohibited and 
restricted therapy during the study.
2.
Agree to follow all requirements that must be met during the study as noted in the 
Inclusion and Exclusion Criteria (eg, contraceptive requirements).
5.4.
Screen Failures
Subject Identification, Enrollment, and Screening Logs
The investigator agrees to complete a subject identification and enrollment log to permit easy 
identification of each subject during and after the study. This document will be reviewed by the 
sponsor study-site contact for completeness.
The subject identification and enrollment log will be treated as confidential and will be filed by 
the investigator in the study file. To ensure subject confidentiality, no copy will be made. All 
reports and communications relating to the study will identify subjects by subject identification 
and date of birth (as allowed by local regulations). In cases where the subject is not randomized 
into the study, the date seen and date of birth (as allowed by local regulations) will be used.
The total screening period is 28 days. All screening tests should be performed within 28 days prior 
to end of screening period unless specified in the Schedule of Activities (Table 2 to 
Table 4). 
Screen Failures
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. Rescreening must be discussed with and approved by the sponsor on a case-by-case 

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Refer to local prescribing information for dexamethasone for complete information on warnings, 
precautions and patient management during treatment.
6.1.2.
Bortezomib
For subjects on Arm A receiving bortezomib as part of the standard therapy PVd (21-day cycles), 
bortezomib will be administered at 1.3 mg/m2 SC twice weekly for 2 weeks (Days 1, 4, 8, and 11) 
followed by a 10-day rest period (Days 12 to 21) in Cycle 1 to 8. Starting with Cycle 9, bortezomib
will be administered weekly on Days 1 and 8, followed by a 13-day rest period (Days 9 to 21). At 
least 72 hours should elapse between consecutive doses of bortezomib.
For subjects on Arm B receiving bortezomib as part of the bridging therapy PVd (21-day cycles), 
bortezomib will be administered at 1.3 mg/m2 SC on Days 1, 4, 8, and 11. Additional cycles of 
bridging therapy may be considered based on subject’s clinical status and timing of availability of 
JNJ-68284528. Investigator must contact the sponsor for approval.
Refer to local prescribing information for bortezomib for complete information on warnings, 
precautions and patient management during treatment.
6.1.3.
Daratumumab
For subjects on Arm A receiving daratumumab as part of the standard therapy DPd (28-day cycles),
daratumumab will be administered SC at a dose of 1800 mg weekly on Days 1, 8, 15, and 22 for 
initial 2 cycles, then every 2 weeks on Days 1 and 15 for Cycles 3 to 6, and then every 4 weeks on
Day 1 starting with Cycle 7.
For subjects on Arm B receiving daratumumab as part of the bridging therapy DPd (28-day cycles),
daratumumab will be administered SC at a dose of 1800 mg weekly. Additional cycles of bridging 
therapy may be considered based on subject’s clinical status and timing of availability of 
JNJ-68284528. Investigator must contact the sponsor for approval.
Refer to the Investigational Product Preparation Instructions (IPPI) for additional guidance on 
administration of daratumumab SC.
Refer to local prescribing information for daratumumab for complete information on warnings, 
precautions and patient management during treatment.
6.1.4.
Pomalidomide 
For subjects on Arm A receiving pomalidomide as part of the standard therapy PVd, pomalidomide 
will be administered at a dose of 4 mg/day PO on Days 1 to 14 of each 21-day cycle. For subjects 
receiving pomalidomide as part of DPd, pomalidomide will be administered at a dose of 4 mg/day 
PO on Days 1 to 21 of each 28-day cycle.
For subjects on Arm B receiving pomalidomide as part of the bridging therapy PVd, pomalidomide 
will be administered at a dose of 4 mg/day on Days 1 to 14. For subjects on Arm B receiving 
pomalidomide as part of DPd, pomalidomide will be administered at a dose of 4 mg/day on Days 
1 to 21.

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Refer to local prescribing information for pomalidomide for complete information on warnings, 
precautions and patient management during treatment.
6.1.5.
JNJ-68284528
6.1.5.1.
Apheresis and Bridging Therapy
Subjects randomized to Arm B will undergo apheresis 3 to 6 days after randomization. If for 
logistical reasons apheresis cannot be performed 3-6 days after randomization, shorter timeframe 
will be accepted when possible. If apheresis is delayed after randomization, the sponsor should be 
notified. Bridging therapy with PVd or DPd, as determined by investigator’s choice prior to 
screening, should be started after apheresis but no more than 7 days after randomization. The 
investigator must contact the sponsor for approval. Additional cycles of bridging therapy may be 
considered based on subject’s clinical status and timing of availability of JNJ-68284528. 
6.1.5.2.
Criteria for Apheresis
The investigator should contact the sponsor if evidence of rapid disease progression or suspected 
CNS involvement is observed between randomization and apheresis. Subjects must meet the 
following criteria to proceed with apheresis:
!
Hemoglobin ≥8 g/dL (PRBC transfusion is permitted)
!
Platelet count ≥50 × 109/L (platelet transfusion is permitted)
!
Negative pregnancy test for women of childbearing potential up to 72 hours prior to apheresis
!
No use of supplemental oxygen to maintain oxygen saturation
!
ECOG performance status grade of 0 or 1
!
No investigational agents and anti-myeloma therapy within the timeframe as detailed in the 
exclusion criteria 
!
No focal radiotherapy as specified in the exclusion criteria, except palliative radiotherapy for 
symptomatic management of bone disease
!
No evidence of serious active viral, bacterial, or uncontrolled systemic fungal infection. 
Subjects on anti-infective agents within 7 days prior to apheresis must receive approval to 
proceed from sponsor
!
No major surgery as specified in the exclusion criteria
!
No live, attenuated vaccines as specified in the exclusion criteria
!
No new arrhythmia or other cardiac adverse events unless controlled with medical 
management and approved by the medical monitor
For subjects who require a repeat apheresis, the following assessments should be collected before 
the second apheresis: weight, hematology laboratory assessments, chemistry laboratory 
assessments, and echocardiogram or MUGA (if clinically indicated). Blood samples for biomarker
assessments including immunophenotyping and CyTOF/PBMC (TCR Seq)/Plasma) should also 
be collected.

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6.1.5.3.
Conditioning Regimen
After completion of PVd or DPd bridging therapy, and after the site is notified in writing by the 
sponsor that manufacture and quality testing of JNJ-68284528 has been completed, each subject 
will receive a conditioning regimen of IV cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2
for 3 doses. Sponsor approval must be obtained to change the conditioning regimen schedule. The 
dose of fludarabine should be reduced to 24 mg/m2 for subjects with an eGFR of 30 to 
70 mL/min/1.73 m2. Cyclophosphamide and fludarabine should be administered using 
administration procedures and supportive care according to the site’s standard of care. 
JNJ-68284528 should be administered as described in the cell therapy product procedures manual 
(CTPPM) and IPPI. JNJ-68284528 will be administered as a single infusion 5 to 7 days after the 
start of the conditioning regimen (the first day of conditioning is Day -7 to Day -5, and the day of 
JNJ-68284528 infusion is Day 1).
Exceptional Release Criteria
In the event a JNJ-68284528 product is manufactured that does not meet pre-specified release 
criteria or protocol-defined maximum total cell dose, the sponsor will evaluate the risk/benefit for 
administration of the affected product and determine if the supply of the product to the treating 
physician could be considered. If required, approval from the relevant health authorities for use of 
the product will be obtained in compliance with local regulations regarding notification and 
approval. In the event the supply of the affected product is deemed appropriate by the sponsor and 
requested by the investigator, the investigator will discuss with the subject the potential risks and 
benefits of receiving the affected product and treatment alternatives. Products provided through 
this exceptional release or similar process that exceed the protocol maximum dose will not qualify 
for overdose reporting.  
6.1.5.4.
Criteria for Conditioning Regimen (Cyclophosphamide and 
Fludarabine) Dosing
The investigator should contact the sponsor if evidence of rapid disease progression or significant 
change in the subject’s clinical status is observed after bridging therapy and before the start of the 
conditioning regimen. In addition, subjects must meet the following criteria to proceed with 
cyclophosphamide and fludarabine dosing:
!
Transfusion support is permitted to maintain a hemoglobin of ≥8 g/dL as needed, and platelets 
of ≥50 x 109/L until 3 days before the hematology laboratory test, preceding lymphodepletion;
!
Myeloid growth factors are permitted at investigator’s discretion up to 1 day prior to the start 
of the conditioning regimen. Pegylated myeloid growth factors (ie, pegfilgrastim) are 
prohibited;
!
Estimated glomerular filtration rate ≥30 mL/min per 1.73 m2. The dose of fludarabine should 
be reduced according to the guidance in Section 6.1.5.3;
!
The investigator must contact the sponsor if the subject has any sign of a reduction in kidney 
function, which may be manifested by a clinically significant increase in serum creatinine, a
clinically significant decrease in eGFR, and/or a clinically significant decrease in urine output 
compared to baseline;

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!
ECOG performance status grade of 0 or 1;
!
Aspartate aminotransferase (AST) #3 × ULN;
!
Alanine aminotransferase (ALT) #3 × ULN;
!
Total bilirubin #2.0 × ULN; except in subjects with congenital bilirubinemia, such as Gilbert 
syndrome (in which case direct bilirubin #1.5 × ULN is required);
!
Negative pregnancy test for women of childbearing potential up to 72 hours prior to the first 
dose of the conditioning regimen;
!
Subjects may not have received the following prior to the start of the conditioning regimen:
)
Daratumumab within 21 days;
)
Bortezomib within 14 days;
)
Pomalidomide within 7 days;
)
Dexamethasone within 7 days
!
No active non-hematologic Grade ≥3 toxicity secondary to bridging therapy;
!
No live, attenuated vaccines within 6 weeks prior to conditioning regimen;
!
No signs of infection. For subjects requiring systemic anti-microbial treatment or with 
temperature >38.0°C/100.4°F within 7 days prior to the first dose of conditioning regimen, 
the investigator must receive approval to proceed from the sponsor;  
!
No cumulative dose of corticosteroids equivalent to ≥70 mg prednisone within the 7 days prior 
to conditioning regimen dosing. The sponsor should be called for approval if a subject receives 
corticosteroids at a dose equivalent to >10 mg prednisone per day in the week prior to the start 
of the conditioning regimen;
!
No use of supplemental oxygen to maintain oxygen saturation;
!
No new arrhythmia or other cardiac adverse events unless controlled with medical 
management and approved by the medical monitor.
6.1.5.5.
Evaluation Prior to Administration of JNJ-68284528
JNJ-68284528 Dosing Delays: 
Subjects will be evaluated for safety on the day of JNJ-68284528 infusion. If a significant health 
status change (eg, clinical deterioration, rapidly progressing disease) occurs following the start of 
the conditioning regimen (see Section 6.1.5.4), the investigator should contact sponsor prior to 
dosing.
Infusion of JNJ-68284528 must be delayed if any of the following events occur:
!
Signs of active infection: Do not administer JNJ-68284528 to subjects with active infection. 
For subjects requiring systemic anti-microbial treatment, or 
with temperature 
≥38.0°C/100.4°F within 48 hours before JNJ-68284528 infusion, investigator must consult 
with the sponsor prior to dosing. 

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Table 10:
JNJ-68284528 Administration
Dose
JNJ-68284528 will be administered in one infusion. The target dose is 0.75 x 106
CAR-positive viable T cells/kg (range: 0.5-1.0 x 106 CAR-positive viable T cells/kg) as 
described in Section 4.3.3. The maximum total dose of cells to be administered to any subject 
is 1.0 x 108 CAR-positive viable T cells (ie, the maximum weight adjusted dose calculated for 
a 100-kg subject). Product will be manufactured based on weight at apheresis.
If after apheresis and CAR-T cell preparation the quantity of JNJ-68284528 manufactured is 
not sufficient for dosing at the lower end of the dosing range, dosing for that subject may 
proceed, provided that a measurable quantity of JNJ-68284528 CAR-positive viable T cells 
that pass quality testing are generated and product is released per company exceptional release 
procedures (see Section 6.1.5.3). In case the quantity of cilta-cel manufactured exceeds the 
upper end of the dosing range, it will be evaluated similarly per company exceptional release 
procedures or similar process (see Section 6.1.5.3).
Route/Regimen
JNJ-68284528 IV infusion is to be administered under the supervision of site staff. Refer to 
the IPPI for JNJ-68284528 infusion instructions.
NOTE: tocilizumab must be available on-site before the start on an infusion.
Dosing Instructions
The actual dose for study treatment administration will be based on the subject’s weight (kg; 
to 1 decimal place) at apheresis. 
Schedule of 
Administration
One intravenous infusion
Hospitalization 
Requirements
Dependent on the subject’s status, medical history, concurrent comorbidities, adequate social 
support (full-time company of a competent adult) or potential risk factors for developing 
CAR-T toxicities, including CRS and neurotoxicity, it will be at the Investigator’s discretion 
and subject’s willingness whether the subject: 
•
will be admitted for inpatient monitoring from the day of infusion (Day 1) through Day 14 
of JNJ-68284528 infusion (with potential discharge on Day 10 if there are no CRS, 
neurotoxicity or other clinically significant events),
OR 
•
will receive JNJ-68284528 infusion as an outpatient in close proximity (within 30 min) to 
the hospital, be monitored for outpatient follow-up and then be admitted for the required 
inpatient monitoring from Day 5 to Day 14 after JNJ-68284528 infusion (with potential 
discharge on Day 10 if there are no CRS, neurotoxicity or other clinically significant 
events)
This evaluation should occur at the time of apheresis, prior to administration of the 
conditioning regimen and again prior to JNJ-68284528 infusion, and in consultation and with 
approval from the sponsor to determine whether outpatient administration and follow-up after 
JNJ-68284528 infusion is suitable for a given subject and site. The patient must be clinically 
evaluated after JNJ-68284528 infusion for at least 6 hours before being discharged from the 
outpatient facility
Subject to institutional guidance, local regulations, investigator discretion and sponsor 
approval, if outpatient JNJ-68284528 administration is being considered, please refer to 
Section 10.16 (JNJ-68284528 Outpatient Administration Guidelines) and Schedule of 
Activities (Table 5).
For countries or specific hospitals which require hospitalization for all patients treated with 
cellular therapy, the more stringent requirements for hospitalization will prevail
Subjects will be asked to remain within a 1-hour travel time of the hospital and in the 
company of a competent adult at all times for 1 additional week after hospital discharge, or 
until study Day 21, whichever is sooner.  
At the first sign of CRS (such as fever), subjects should be immediately hospitalized for 
evaluation. Further details regarding management of CRS are described in Table 11.
Hospitalization is required for Grade 2, 3, or 4 CAR-T cell-related neurotoxicity (eg, ICANS)
temporally associated to CRS. Further details regarding management of ICANS are described 
in Table 12.

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Table 10:
JNJ-68284528 Administration
Hospitalization for neurotoxicity that is not temporarily associated with CRS, or any other 
neurologic adverse events, is at the discretion of the investigator.
Vital Sign and Clinical 
Safety Monitoring
Monitor vital signs as indicated in the Schedule of Activities (Table 5)
CAR=chimeric antigen receptor; CRS=cytokine release syndrome
6.1.6.
Management Guidelines for Potential Risks of JNJ-68284528
6.1.6.1.
Management of Cytokine Release Syndrome 
In the Legend-2 study, CRS was reported in approximately 92% of subjects who received 
LCAR-B38M CAR-T cells. Most CRS events were Grade 1 or Grade 2. All events of CRS started 
with fever after the infusion of CAR-T therapy (see Section 2.2.5). Of the subjects who developed 
CRS, approximately 84% experienced transiently increased AST. AST increase was Grade 3 or 
Grade 4 in 31% and 6% of subjects with CRS, respectively. If CRS is suspected, subjects should 
be monitored for increased AST, and consumptive coagulopathy, indicated by an increase in 
D-dimers and a decrease in fibrinogen.
As of the 1 September 2020 data cutoff, CRS was reported for 92 of 97 subjects (94.8%) who 
received JNJ-68284528 in Study 68284528MMY2001. Most subjects (87 subjects ∃89.7%%) 
experienced CRS AEs that were Grade 1 or2, 3 (3.1%) subjects experienced Grade 3 CRS, 1 
subject experienced Grade 4 CRS, and 1 subject experienced Grade 5 CRS (see Section 2.2.5).
Symptoms indicative of CRS may include, but are not limited to, fever (with or without rigors), 
arthralgia, nausea, vomiting, tachypnea, hypoxia, tachycardia, hypotension, headache, confusion, 
tremor, delirium, dyspnea, pulmonary edema, and capillary leak.24 Potentially life-threatening 
complications of CRS may include cardiac dysfunction, adult respiratory distress syndrome, 
neurologic toxicity, renal failure, hepatic failure, and disseminated intravascular coagulation.
Laboratory testing to monitor for disseminated intravascular coagulation, a manifestation of CRS, 
should be carried out in addition to daily monitoring of chemistry and hematology assessments 
(including ferritin and C-reactive protein [CRP]) when fever or other signs of potential CRS are 
present (see Table 11). In addition, pulmonary, renal and hepatic function will be monitored 
closely (see Table 11). Cytokine release syndrome will be captured as an adverse event of special 
interest (see Section 8.3.1).
Rarely, severe CRS can evolve into a presentation consistent with hemophagocytic 
lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) that may require additional 
therapy. In these cases, laboratory testing may reveal high serum levels of ferritin, lactate 
dehydrogenase, triglycerides, soluble CD25, and cytokines (such as IFNγ and IL-6), and low serum 
levels of fibrinogen.30 Severe thrombocytopenia, low fibrinogen, and often DIC may be features 
of HLH, all of which combined may increase the risk of severe bleeding in these subjects. If HLH 
is suspected, anticoagulation should be avoided or modified based on institutional guidelines 
depending on platelet count and renal function. Subjects with HLH should have their platelet count 
and coagulation parameters very closely monitored and maximal support should be provided to 

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avoid major bleeding complications. For example, consider platelet transfusion if platelets are less 
than 50 × 109/L. Under these circumstances, investigators should consider treating the subject in 
the ICU, so that maximal monitoring and support can be carried out during this period.
Trained clinical personnel should be prepared to intervene in the event of CRS. Resources 
necessary for resuscitation (ie, agents such as epinephrine and aerosolized bronchodilator, medical 
equipment such as oxygen, tracheostomy equipment, and a defibrillator) should be readily 
available. Tocilizumab must be available on-site prior to administration of JNJ-68284528. Vital 
signs and laboratory parameters must be monitored at regular intervals until normal. Additional 
specimens for pharmacokinetic and biomarker testing should be collected as per the schedule 
outlined in the Schedule of Activities (Table 5).
Infection and CRS may have a similar presentation. Therefore, investigators are strongly 
encouraged to evaluate for an infection at the first signs or symptoms of CRS. Cultures and 
imaging should be obtained: the clinical signs and symptoms should determine which tests are 
appropriate. 
Recommendations for the clinical management of CRS are provided in Table 11. At the first sign 
of CRS (such as fever), subjects should be immediately hospitalized for evaluation. The use of 
myeloid growth factors, particularly G-CSF, should be avoided during CRS. Tocilizumab 
intervention may be considered with presenting symptom of fever in the absence of clear infectious 
etiology. Early tocilizumab should be considered in subjects at high risk of severe CRS (for 
example, high baseline tumor burden, early fever onset, or persistent fever after 24 hours of 
symptomatic treatment). Other cytokine targeting therapies (for example, IL1 and/or anti-TNFα) 
may be used based on institutional practice, especially for cases of CRS which does not respond 
to tocilizumab and corticosteroids. Therapy directed at reduction or elimination of CAR-T cells, 
including chemotherapy, may be considered in consultation with the sponsor for subjects who 
develop high-grade CRS with laboratory findings overlapping with HLH/MAS (including 
hyperferritinemia) that remains severe or life-threatening following prior therapies, including 
tocilizumab and corticosteroids.
Table 11:
Guidelines for the Management of Cytokine Release Syndrome
CRS Gradea
Tocilizumabb
Corticosteroidsf
Grade 1 
Temperature ≥38°Cc
Tocilizumab 8 mg/kg i.v. over 1 hour 
(not to exceed 800 mg) may be 
considered
NA
Grade 2 
Symptoms require and respond to moderate 
intervention. 
Temperature ≥38°Cc with:
Hypotension not requiring vasopressors,
and/or,
Hypoxia requiring oxygen via canulae or 
blow-by,
Administer tocilizumab 8 mg/kg i.v. 
over 1 hour (not to exceed 800 mg).
Repeat tocilizumab every 8 hours as 
needed if not responsive to i.v. fluids 
up to 1 liter or increasing 
supplemental oxygen.
Consider methylprednisolone 
1 mg/kg i.v. twice daily or equivalent 
dexamethasone (eg, 10 mg i.v. every 
6 hours).
If no improvement within 24 hours or rapid progression, repeat tocilizumab 
and escalate dose and frequency of dexamethasone (20 mg i.v. every 6 to 
12 hours).
After 2 doses of tocilizumab, consider alternative anticytokine agents.d

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Table 11:
Guidelines for the Management of Cytokine Release Syndrome
CRS Gradea
Tocilizumabb
Corticosteroidsf
or, 
Grade 2 organ toxicity.
Do not exceed 3 doses of tocilizumab in 24 hours, or 4 doses in total.
Grade 3 
Symptoms require and respond to 
aggressive intervention. 
Temperature ≥38°Cc with:
Hypotension requiring 1 vasopressor with 
or without vasopressin,
and/or,
Hypoxia requiring oxygen via high-flow 
nasal canulae, facemask, nonrebreather 
mask, or Venturi mask, 
or, 
Grade 3 organ toxicity or Grade 4 
transaminitis.
Per Grade 2 
Administer methylprednisolone 
1 mg/kg i.v. twice daily or equivalent 
dexamethasone (eg, 10 mg i.v. every 
6 hours).
If no improvement within 24 hours or rapid progression, repeat tocilizumab 
and escalate dose and frequency of dexamethasone (20 mg i.v. every 6 to 
12 hours).
If no improvement within 24 hours or continued rapid progression, switch to 
methylprednisolone 2 mg/kg i.v. every 12 hours.
After 2 doses of tocilizumab, consider alternative anticytokine agents.d
Do not exceed 3 doses of tocilizumab in 24 hours, or 4 doses in total.
Grade 4 
Life-threatening symptoms. 
Requirements for ventilator support, 
CVVHD. 
Temperature ≥38°Cc with:
Hypotension requiring multiple 
vasopressors (excluding vasopressin),
and/or,
Hypoxia requiring positive pressure 
(eg, CPAP, BiPAP, intubation, and 
mechanical ventilation),
or,
Grade 4 organ toxicity (excluding 
transaminitis).
Per Grade 2 
Administer dexamethasone 20 mg i.v. 
every 6 hours.
After 2 doses of tocilizumab, consider alternative anticytokine agents.d
Do not exceed 3 doses of tocilizumab in 24 hours, or 4 doses in total.
If no improvement within 24 hours, consider methylprednisolone (1-2 g i.v., 
repeat every 24 hours if needed; taper as clinically indicated) or other 
immunosuppressants (eg, other anti-T-cell therapies).
ASTCT=American Society for Transplantation and Cellular Therapy; BiPAP=bilevel positive airway pressure; 
CPAP=continuous positive airway pressure; CVVHD=continuous veno-venous hemodialysis; i.v.=intravenous(ly); NA=not 
applicable.
a
Based on ASTCT consensus grading (Lee 2019), modified to include organ toxicity.
b
Refer to tocilizumab prescribing information for details.
c
Attributed to CRS. Fever may not always be present concurrently with hypotension or hypoxia, as it may be 
masked by interventions such as antipyretics or anticytokine therapy (eg, tocilizumab or steroids). Absence of 
fever does not impact CRS management decision. In this case, CRS management is driven by hypotension 
and/or hypoxia and by the more severe symptom not attributable to any other cause.
d
Monoclonal antibodies targeting cytokines may be considered based on institutional practice for unresponsive 
CRS.
e
Low-flow nasal cannula is ≤6 L/min; high-flow nasal cannula is >6 L/min.
f
Continue corticosteroids use until the event is ≤Grade 1; taper steroids if total corticosteroid exposure is greater 
than 3 days.
Supportive care for CRS (including but not limited to anti-pyretic agents, IV fluid support, 
vasopressors, supplemental oxygen, etc.) should be administered according to the clinical 

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manifestations of the subject’s illness. Similarly, ancillary testing such as B-type natriuretic 
peptide assessment, echocardiograms, arterial blood gas, assessments of coagulation laboratory 
tests, liver and renal function, etc, should be performed if clinically indicated.
6.1.6.2.
Neurologic Toxicities
Based on the specific mode-of-action of JNJ-68284528, severe or serious neurologic toxicities 
(including CAR-T cell-related neurotoxicity, ie, Immune Effector Cell-Associated Neurotoxicity 
Syndrome [ICANS]) may occur (Section 6.1.6.2.1). Subjects should be monitored for 
neurotoxicity for 1-year post JNJ-68284528 infusion (Section 6.1.6.2.2).
6.1.6.2.1.
CAR-T Cell-related Neurotoxicity (Immune Effector Cell-Associated 
Neurotoxicity Syndrome [ICANS])
Subjects should have the Immune Effector Cell-associated Encephalopathy (ICE) Assessment 
Tool (ICE-Tool; Section 10.15) performed within 24 hours prior to infusion of JNJ-68284528 and 
daily after the first symptoms of CAR-T cell related neurotoxicity (ie, ICANS) are suspected and 
until resolution. Consider performing ICE-Tool more frequently until neurotoxicity symptoms 
resolve. Consider performing neuroimaging (eg, MRI) at screening and/or neurology consultation 
if pre-existing disease is suspected; see Section 8.1.6, Safety Assessments.
Subjects should be monitored for neurologic toxicities including, but not restricted to, speech 
disorders, aphasia, convulsions, disturbances in consciousness, confusion, disorientation, or 
coordination and balance disorders. If these or other neurologic toxicities are observed, regardless 
of causality, then the sponsor’s medical monitor must be consulted. Hospitalization is required for 
Grade 2, 3, or 4 CAR-T cell-related neurotoxicity (ie, ICANS) temporally associated with CRS.
At the first sign of neurotoxicity, neurology consultation and evaluation should be considered. 
Rule out alternative etiologies including infectious etiologies (eg, viral origin such as human 
herpesvirus (HHV) HHV-6, HHV-7) if clinically indicated. Subjects who have a lumbar puncture 
as part of their neurologic work up should have a sample of cerebral spinal fluid also sent for 
additional testing by the sponsor. For signs of seizures or raised intracranial pressure/cerebral 
edema, consider neuroimaging (computed tomography [CT]/MRI), transfer the subject to the 
intensive care unit and treat according to institutional guidelines or practices.
General management for CAR-T cell-related neurotoxicity (ie, ICANS) with or without concurrent 
CRS is summarized in Table 12. All neurologic adverse events, including CAR-T related 
neurotoxicity (ie, ICANS), will be captured as an adverse event of special interest (see 
Section 8.3.1).
If concurrent CRS is suspected during the neurologic toxicity event, administer:
!
Corticosteroids according to the more aggressive intervention based on the CRS and 
neurologic toxicity grades in Table 11 and Table 12
!
Tocilizumab according to CRS grade in Table 11
!
Antiseizure medication according to neurologic toxicity in Table 12

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Table 12:
Guidelines for the Management of Immune Effector Cell-Associated Neurotoxicity Syndrome
(ICANS) 
ICANS Gradea
Corticosteroids
Grade 1
ICE score 7-9b
or depressed level of consciousness: awakens 
spontaneously.
Consider dexamethasonec 10 mg i.v. every 6 to 12 hours for 2 to 
3 days
Consider nonsedating, antiseizure medicines (eg, levetiracetam) for 
seizure prophylaxis.
Grade 2
ICE score-3-6b
or depressed level of consciousness: awakens to voice
Administer dexamethasonec 10 mg i.v. every 6 hours for 2 to 
3 days, or longer for persistent symptoms.
Consider steroid taper if total corticosteroid exposure is greater than 
3 days.
Consider nonsedating, antiseizure medicines (eg, levetiracetam) for 
seizure prophylaxis.
Grade 3
ICE score-0-2b
(If ICE score is 0, but participant is arousable 
(eg, awake with global aphasia) and able to perform 
assessment)
or depressed level of consciousness: awakens only to 
tactile stimulus,
or seizures, either:
! any clinical seizure, focal or generalized, that resolves 
rapidly, or
! nonconvulsive seizures on EEG that resolve with 
intervention,
or raised ICP: focal/local edema on neuroimaging.d
Administer dexamethasonec 10 mg to 20 mg i.v. every 6 hours.
If no improvement after 48 hours or worsening of neurologic 
toxicity, escalate dexamethasonec dose to at least 20 mg i.v. every 
6 hours; taper within 7 days, 
or escalate to high-dose methylprednisolone (1g/day, repeat every 
24 hours if needed; taper as clinically indicated).
Consider nonsedating, antiseizure medicines (eg, levetiracetam) for 
seizure prophylaxis.
Grade 4
ICE score-0b (participant is unarousable and unable to 
perform ICE assessment),
or depressed level of consciousness, either:
! participant is unarousable or requires vigorous or 
repetitive tactile stimuli to arouse, or
! stupor or coma,
or seizures, either:
! life-threatening prolonged seizure (>5 min), or
! repetitive clinical or electrical seizures without return 
to baseline in between,
or motor findingse:
! deep focal motor weakness such as hemiparesis or 
paraparesis,
or raised ICP/cerebral edema, with signs/symptoms such 
as:
! diffuse cerebral edema on neuroimaging, or
! decerebrate or decorticate posturing, or
! cranial nerve VI palsy, or
! papilledema, or
! Cushing’s triad.
Administer dexamethasonec 10 mg to 20 mg i.v. every 6 hours.
If no improvement after 24 hours or worsening of neurologic 
toxicity, escalate to high-dose methylprednisolone (1-2 g/day, 
repeated every 24 hours if needed; taper as clinically indicated). 
Consider nonsedating, antiseizure medicines (eg, levetiracetam) for 
seizure prophylaxis.
If raised ICP/cerebral edema is suspected, consider hyperventilation 
and hyperosmolar therapy. Give high-dose methylprednisolone 
(1-2 g/day, repeat every 24 hours if needed; taper as clinically 
indicated), 
and 
consider 
neurology 
and/or 
neurosurgery 
consultation.

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Table 12:
Guidelines for the Management of Immune Effector Cell-Associated Neurotoxicity Syndrome
(ICANS) 
ASTCT=American Society for Transplantation and Cellular Therapy; EEG=electroencephalogram; i.v.=intravenous(ly).
Note: ICANS grade and management is determined by the most severe event (ICE score, level of consciousness, seizure, 
motor findings, raised ICP/cerebral edema), not attributable to any other cause.
a
Based on ASTCT consensus grading (Lee 2019).
b
If participant is arousable and able to perform ICE assessment, assess: Orientation (oriented to year, month, 
city, hospital =4 points); Naming (name 3 objects, eg, point to clock, pen, button =3 points); Following 
Commands (eg, “show me 2 fingers” or “close your eyes and stick out your tongue” =1 point); Writing
(ability to write a standard sentence =1 point); and Attention (count backwards from 100 by 10 =1 point) (see 
Section 10.15). If participant is unarousable and unable to perform ICE assessment (Grade 4 ICANS) 
=0 points.
c
All references to dexamethasone administration are dexamethasone or equivalent.
d
Intracranial hemorrhage with or without associated edema is not considered a neurotoxicity feature and is 
excluded from ICANS grading. It may be graded according to CTCAE version 5.0.
e
Tremors and myoclonus associated with immune effector cell therapies may be graded according to CTCAE 
version 5.0, but they do not influence ICANS grading.
Table 13:
Guidelines for the Management of Raised Intracranial Pressure (ICP) / Cerebral Edemaa
!
Elevate head of subject’s bed to an angle of 30 degrees.
!
If subject has Ommaya reservoir, drain cerebral spinal fluid to target opening pressure of <20 mmHg.
!
Hyperventilation to achieve target partial pressure of arterial carbon dioxide (PaCO2) of 28 to 30 mmHg, but 
maintained for no longer than 24 hours.
!
Consider neurology and/or neurosurgery consultation.
!
Use high-dose corticosteroids with methylprednisolone IV 1 g/day, as recommended above.
!
Hyperosmolar therapy with either mannitol (20 g/dL solution) or hypertonic saline (3% or 23.4%, as detailed 
below):
o
Mannitol: initial dose 0.5 to 1 g/kg; maintenance at 0.25 to 1 g/kg every 6 hours while monitoring 
metabolic profile and serum osmolality every 6 hours, and withhold mannitol if serum osmolality is ≥320 
mOsm/kg, or the osmolality gap is ≥40,
o
Hypertonic saline: initial 250 ml of 3% hypertonic saline; maintenance at 50 to 75 mL/hour while 
monitoring electrolytes every 4 hours, and withhold infusion if serum Na levels reach ≥155 mEq/L,
o
For subjects with imminent herniation: initial 30 mL of 23.4% hypertonic saline; repeat after 15 min, if 
needed.
!
Consider IV anaesthetics for burst-suppression pattern on electroencephalography.
a
In addition to toxicity management guidelines provided in Table 12: Guidelines for the Management of Immune Effector 
Cell-Associated Neurotoxicity Syndrome (ICANS)
6.1.6.2.2.
Other Neurotoxicities
If other neurotoxicities characterized by movement and neurocognitive TEAEs noted below are 
observed, the medical monitor should be contacted, and the subject should be referred immediately 
to a neurologist for a full evaluation. Particular attention should be paid to the appearance of any 
of the following:
!
movement impairments (eg, micrographia or changes in handwriting, tremors, bradykinesia, 
rigidity, shuffling gait, impaired balance and coordination, difficulty writing, difficulty 
performing activities of daily living like dressing or feeding oneself), 
!
cognitive impairments (eg, memory loss or forgetfulness, disturbances in attention, mental 
slowness or fogginess, difficulty speaking or slurred speech, difficulty reading or 
understanding words), 

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!
personality change (eg, reduced facial expression, flat affect, reduced ability to express 
emotions, less communicative, disinterest in activities)
Additional monitoring and mitigation strategies include enhanced bridging therapy to reduce 
baseline tumor burden, early aggressive treatment of CRS and ICANS, handwriting assessments 
for early detection of neurotoxicity symptoms, and extended monitoring and reporting time for 
neurotoxicity for the duration of study.
Early detection, workup and intervention, may be important to prevent neurologic toxicity from 
worsening. The following is a list of potential diagnostics that should be considered in subjects 
with new neurologic symptoms:
!
Positron emission tomography/computerized tomography (PET/CT) of the brain and/or brain 
MRI with perfusion and an electroencephalogram (EEG).
!
Lumbar puncture to rule out infection (in particular John Cunningham virus [JCV], herpes 
zoster virus [HZV], herpes simplex virus [HSV]-1/2, HHV-6, HHV-7, Epstein-Barr virus 
[EBV], cytomegalovirus [CMV]).
!
Serologic testing for HHV-6 and HHV-7 by PCR for viremia. 
!
CSF flow cytometry and cytology should be considered to rule out leptomeningeal disease. 
!
Cerebral spinal fluid (CSF) analysis to rule out paraneoplastic syndromes. 
!
Thiamine level (consider empiric thiamine replacement while awaiting results)
(MD Anderson 2019)28
Other cytokine-targeting therapies (for example, IL-1) may be used based on institutional practice, 
especially for cases of neurotoxicity which does not respond to tocilizumab or corticosteroids. 
Therapy directed at reduction or elimination of CAR-T cells, including chemotherapy, may be 
considered in consultation with the sponsor for subjects who develop neurotoxicity that remains 
unresponsive to other interventions.
Per Section 8.9 of the protocol, if cerebral spinal fluid (CSF) or other relevant biological sample 
analysis is clinically indicated, these samples will be requested for additional analysis by the 
sponsor.
6.1.6.3.
Tumor Lysis Syndrome
Although tumor lysis syndrome is uncommon in subjects with MM, one subject in the Phase 1 
Legend-2 Study experienced fatal tumor lysis syndrome. Subjects must be monitored closely for 
symptoms of tumor lysis syndrome. It is also strongly recommended that high-risk subjects, 
ie, those with a high tumor burden (≥60% plasma cell infiltrate on the bone marrow biopsy or 
aspirate [whichever is higher] or a subject with multiple extramedullary disease sites or 
plasmacytomas), be treated prophylactically in accordance with local standards (eg, extra 
hydration; diuretics; allopurinol 300 mg daily or other primary or secondary uricosuric agents, as 
indicated). 

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6.1.6.4.
Second Primary Malignancy
Second primary malignancy (SPM) is a possibility due to the risk of viral insertion (DNA 
integration) of the lentiviral vector. SPMs should be managed per institutional standards and must 
be reported for the duration of the study in both treatment arms (Arm A and Arm B), irrespective 
of when they occur. In the JNJ-68284528 Treatment Arm (Arm B), SPMs will continue to be 
collected in a long-term follow-up study yearly until 15 years post dosing of JNJ-68284528. For 
subjects in Arm B diagnosed with a SPM, a tumor sample should be collected, and DNA, RNA, 
or protein analysis may be performed to investigate the presence of lentiviral elements. SPM on 
both arms of the study will be captured as an AE of special interest (see Section 8.3.1).
6.1.6.5.
Prolonged Cytopenia
Subjects may exhibit cytopenia for several weeks following lymphodepleting chemotherapy and 
JNJ-68284528 infusion. Prolonged neutropenia may increase the risk of infection. Severe 
thrombocytopenia may increase the risk of bleeding. Monitor hematological parameters and 
provide supportive care (eg, irradiated blood products, granulocyte-colony stimulating factor for 
neutropenia) as outlined by institutional guidelines. Pegylated myeloid growth factors 
(ie, pegfilgrastim) are prohibited within the first 112 days after infusion with JNJ-68284528. The 
use of myeloid growth factors, particularly G-CSF, should be avoided during CRS. Parvovirus 
B19 monitoring by PCR should be considered in subjects experiencing prolonged neutropenia or 
a decline in neutrophil counts following recovery.
6.1.6.6.
Hypogammaglobulinemia
Hypogammaglobulinemia 
may 
occur 
in 
subjects 
receiving 
JNJ-68284528. 
Monitor 
immunoglobulin levels after treatment as detailed in the Schedule of Activities (Table 4 and
Table 5) and more frequently if clinically indicated for safety and treat according to local 
guidelines, including administration of immunoglobulin replacement and monitoring for infection. 
Subjects with IgG <400 mg/dL or recurrent infections (including HBV reactivation) should be 
considered for prophylactic IV or SC IgG as per institutional guidelines. Vaccination with live,
attenuated virus vaccines is prohibited for at least 6 weeks prior to the start of the conditioning 
regimen and for at least 112 days after infusion of JNJ-68284528.
6.1.6.7.
Serious Infections
Do not administer JNJ-68284528 to subjects with active infection. Administration of 
JNJ-68284528 may increase the risk of infection due to cytopenias and hypogammaglobulinemia. 
Subjects should be monitored frequently for infection and should have blood cultures obtained and 
empiric antibiotics administered per institutional standards. Immunocompromised subjects are at 
risk for opportunistic infections. Prophylactic use of antibiotics, antivirals, and antifungals should 
be considered. Extended use of anti-microbial therapies for at least 6 month (or longer as per 
institutional guidelines) or consistent with post ASCT consensus guidelines after CAR-T dosing 
are recommended (see Section 10.28, Appendix 28). Perform screening for hepatitis B virus, HCV, 
and HIV and monitor as clinically indicated (see HBV monitoring recommendations in 
Section 10.6 and Table 5), and initiate treatment as appropriate. HBV reactivation, in some cases 
resulting in fulminant hepatitis, hepatic failure and death, may occur in subjects treated with drugs 

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directed against B cells such as JNJ-68284528. HBV reactivation has occurred in subjects 
receiving other CAR-T products who appear to have resolved hepatitis B infection. Routinely 
monitor HBV DNA and AST/ALT for subjects with risk of HBV reactivation (Section 10.6 and
Table 5).
Subjects receiving cilta-cel are possibly at a higher risk of severe/fatal outcomes from COVID-19 
infection compared with patients who are receiving standard of care therapy. Subjects should be 
reminded of the importance of vaccines and other preventative measures. Investigators should 
consider prophylaxis (eg, Evusheld, if available) and antiviral medications (eg, Paxlovid, if 
available) for patients diagnosed with COVID-19 infection, as noted in Appendix 10.29.
6.1.6.8.
Hypersensitivity Reactions
Allergic reactions may occur with the infusion of JNJ-68284528. Serious hypersensitivity 
reactions including anaphylaxis, may be due to dimethyl sulfoxide, dextran 40, residual kanamycin 
in JNJ-68284528. Subjects should be treated urgently per institutional standards, avoiding 
corticosteroid use if possible. In the JNJ-68284528 Treatment Arm (Arm B), subjects should 
receive premedication prior to JNJ-68284528 dosing as noted in Section 6.1.5.5.
6.1.7.
Management Guidelines for Daratumumab
6.1.7.1.
Infusion-Related Reaction Management for Daratumumab SC
Subjects who receive daratumumab SC should be observed carefully during study drug 
administrations. Subjects should be observed for 6 hours following Cycle 1 Day 1 daratumumab 
administration at the site where daratumumab is administered. Trained study staff at the clinic 
should be prepared to intervene in case of any IRRs, and resources necessary for resuscitation (eg, 
agents such as epinephrine and aerosolized bronchodilator, also medical equipment such as oxygen 
tanks and a defibrillator) must be available at the bedside. See Section 6.5.1.4 for pre-injection
medications and Section 6.5.1.5
for post-injection medications for subjects receiving 
daratumumab.
If an IRR develops, then daratumumab administration should be temporarily interrupted. Subjects 
who experience adverse events during daratumumab administration must be treated for their 
symptoms. Subjects should be treated with paracetamol (acetaminophen), antihistamine, or 
corticosteroids, as needed. Intravenous saline may be indicated. For bronchospasm, urticaria, or 
dyspnea, subjects may require antihistamines, oxygen, corticosteroids, or bronchodilators. For 
hypotension, subjects may require vasopressors. In the event of a life-threatening IRR (which may 
include pulmonary or cardiac events) or an anaphylactic reaction, daratumumab should be 
discontinued.
Infusion-related Reactions of Grade 1 or Grade 2 for Daratumumab SC
If the investigator assesses a Grade 1-2 IRR to be related to administration of study intervention, 
then the daratumumab administration should be interrupted. When the subject's condition is stable, 
daratumumab administration may be restarted at the investigator's discretion. Refer to the IPPI for
further details regarding continuation of daratumumab administration.

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If the subject experiences a Grade 2 or higher event of laryngeal edema, or a Grade 2 or higher event 
of bronchospasm that does not respond to systemic therapy and does not resolve within 6 hours from 
onset, then the subject must be permanently discontinued from daratumumab treatment.
Infusion-related Reactions of Grade 3 or Higher for Daratumumab SC
For IRR adverse events (other than laryngeal edema or bronchospasm) that are Grade 3, the 
daratumumab administration must be stopped, and the subject must be observed carefully until 
resolution of the adverse event or until the intensity of the event decreases to Grade 1, at which point 
the daratumumab SC administration may be restarted at the investigator’s discretion. Refer to the 
IPPI for further details regarding continuation of daratumumab administration.
If the intensity of the adverse event returns to Grade 3 after restart of the daratumumab 
administration, then the subject must be permanently discontinued from daratumumab treatment.
For IRR adverse events that are Grade 4, the daratumumab administration must be stopped, and the 
subject permanently discontinued from daratumumab treatment.
Recurrent Infusion-related Reactions for Daratumumab SC
If a Grade 3 IRR (or Grade 2 or higher event of laryngeal edema, or a Grade 2 or higher event of 
bronchospasm) recurs during or within 24 hours after a subsequent daratumumab administration, 
the subject must be permanently discontinued from daratumumab treatment.
Local Injection-site Reactions for Daratumumab SC
Injection-site reactions are localized reactions at the injection site. In daratumumab 
Study 54767414MMY1004 Part 1, SC administration of daratumumab in abdominal SC tissue was 
associated with local injection site reactions, such as induration and erythema, in some subjects. The 
reactions usually resolved within 60 minutes. Local injection site reactions should be managed per 
institutional standards.
6.1.7.2.
Infections
Administration of daratumumab may increase the risk of infection. Subjects should be monitored 
frequently for infection and should have blood cultures obtained and empiric antibiotics 
administered per institutional standards. For subjects with evidence of positive HBV serology, 
monitor for clinical and laboratory signs of HBV reactivation during, and for at least 6 months 
following the end of study treatment. Manage patients according to current clinical guidelines. 
Consider consulting a hepatitis disease expert as clinically indicated.
In patients who develop reactivation of HBV while on study treatment, suspend study treatment 
and any concomitant steroids, chemotherapy, and institute appropriate treatment. Resumption of 
study treatment in patients whose HBV reactivation is adequately controlled should be discussed 
with physicians with expertise in managing HBV.

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6.2.
Preparation/Handling/Storage/Accountability
Preparation, handling and Storage
Standard therapy (bortezomib, pomalidomide, daratumumab and dexamethasone)
Refer to the CTPPM for additional guidance on preparation, handling and storage information for 
bortezomib, pomalidomide, and dexamethasone. Refer to the IPPI for additional guidance on 
daratumumab SC preparation, handling and storage.
JNJ-68284528
JNJ-68284528 is provided in a single-dose unit containing CAR-positive viable T cells based on 
the subject weight reported at the time of apheresis.
JNJ-68284528 therapy contains human cells genetically modified with a lentiviral vector. Follow 
local biosafety guidelines applicable for handling and disposal of such products. The product is 
prepared from autologous blood collected by apheresis. JNJ-68284528 may carry a risk of 
transmitting infectious viruses to healthcare professionals handling the product. Accordingly, 
healthcare professionals should employ universal precautions to avoid potential transmission of 
infectious diseases when handling the product.
Detailed instructions for storage conditions and handling will accompany clinical drug supplies to 
the clinical study sites. The storage conditions and expiry dates are indicated on the label. Refer to 
the JNJ-68284528 IPPI for additional guidance on study treatment preparation, handling, and 
storage.
6.2.1.
Accountability
Information in this section relates to study treatment that is supplied to investigational sites from 
the study sponsor.
The investigator is responsible for ensuring that all study treatment received at the site is 
inventoried and accounted for throughout the study. The study treatment administered to the 
subject must be documented on the drug accountability form. All study intervention will be stored 
and disposed of according to the sponsor’s instructions. Study-site personnel must not combine 
contents of the study treatment containers.
The dispensing of study treatment (eg, pomalidomide and oral dexamethasone) to the subject, and 
the return of study treatment from the subject (if applicable), must be documented on the drug 
accountability form. Subjects, or their legally acceptable representatives where applicable, must 
be instructed to return all original containers, whether empty or containing study treatment.
Study treatment must be handled in strict accordance with the protocol and the container label and 
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate 
environmental conditions. Unused study treatment, and study treatment returned by the subject, 
must be available for verification by the sponsor’s study site monitor during on-site monitoring 
visits. The return to the sponsor of unused study treatment will be documented on the drug return 

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form. When the study site is an authorized destruction unit and study treatment supplies are 
destroyed on-site, this must also be documented on the study treatment return form.
Potentially hazardous materials such as used ampules, needles, syringes and vials containing 
hazardous liquids, should be disposed of immediately in a safe manner and therefore will not be 
retained for intervention accountability purposes. 
Study treatment should be dispensed under the supervision of the investigator or a qualified 
member of the study-site personnel, or by a hospital/clinic pharmacist. Study treatment will be 
supplied only to subjects participating in the study. Returned study treatment must not be dispensed 
again, even to the same subject. Whenever a subject brings his or her study treatment (eg, 
pomalidomide or dexamethasone) to the study site for pill count, this is not seen as a return of 
supplies. Study treatment may not be relabeled or reassigned for use by other subjects. The 
investigator agrees neither to dispense the study treatment from, nor store it at, any site other than 
the study sites agreed upon with the sponsor. Further guidance and information for the final 
disposition of unused study treatment are provided in the in the SIPPM and CTPPM.
6.3.
Measures to Minimize Bias: Randomization
Central randomization will be implemented in this study. Subjects will be assigned randomly to 
1 of 2 arms based on a computer-generated randomization schedule prepared before the study by 
or under the supervision of the sponsor. The randomization will be balanced by using randomly 
permuted blocks and will be stratified according to 3 baseline factors: investigator’s choice of PVd
vs. DPd, ISS at screening (I vs. II vs. III), and number of prior lines of therapy (1 vs. 2 or 3).
6.4.
Study Intervention Compliance
Compliance with Dexamethasone and Pomalidomide (Arm A-standard therapy [PVd or 
DPd] and Arm B-bridging therapy [PVd or DPd])
Subjects will be asked to return containers of pomalidomide and dexamethasone at each study 
visit. Pill counts will be used to assess compliance. Additional details are provided in the SIPPM
(CTPPM). 
Compliance with Bortezomib (Arm A-standard therapy [PVd] and Arm B-bridging therapy
[PVd]) and Daratumumab (Arm A-standard therapy [DPd] and Arm B-bridging therapy 
[DPd])
Bortezomib and daratumumab administration will be performed in the controlled environment of 
a qualified clinical site, under the direct observation of qualified study-site personnel. Additional 
details are provided in the SIPPM.
Compliance with Apheresis, Conditioning Regimen, and JNJ-68284528 (Arm B)
Apheresis, infusion of cyclophosphamide and fludarabine, and infusion of JNJ-68284528 will be
performed in the controlled environment of a qualified clinical site, under the direct observation 
of qualified study-site personnel. The details of administration will be recorded in the eCRF 
(including date, dose of cells, start, and stop times of the IV infusion, and volume infused). 

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Precautions associated with the use of the study treatment and concomitant medications will be 
reviewed by the sponsor. 
Refer to the CTPPM for a description of the chain of identity and chain of custody procedures 
associated with apheresis product and JNJ-68284528.
6.5.
Concomitant Therapy
Throughout the study, investigators may prescribe concomitant medications or treatments (except 
for those listed in Section 6.5.3) deemed necessary to provide adequate supportive care. All 
concomitant medications will be recorded during screening. Thereafter, selected concomitant 
medications will be reported. Selected concomitant medications consist of any medication given 
for an adverse event or serious adverse event, therapeutically or prophylactically, including, but 
not limited to:
!
Anti-cytokine or anti-cytokine receptor therapies  
!
Anti-seizure medications
!
Any medication given for prophylaxis or treatment of tumor lysis syndrome
!
Any medication given for prevention or treatment of thromboembolic events
!
Medication for prevention or treatment of daratumumab IRRs
!
Corticosteroids (including prophylactically for blood product administrations, physiologic 
replacement doses, high or stress doses, etc.)
!
Immunosuppressive agents
!
Vaccinations
!
Vasopressors and cardiac inotropic agents (For dose, record only maximum daily rate)
!
Blood products 
!
Growth factors
!
Systemic antimicrobials – given for prophylaxis or treatment
!
Chemotherapy given for CAR-T cell related toxicity
Other:
!
Bisphosphonates 
!
Immunoglobulin therapy
!
Medications listed as prohibited in the protocol
!
Palliative Radiation
!
Pain medication
!
Any treatment given for SPMs
!
Any changes in doses from baseline or newly added concomitant medications to treat new or 
prior known co-morbidities

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In the standard therapy Treatment Arm (Arm A), the recording period is from the signing of the 
ICF until 30 days after the last dose of daratumumab, pomalidomide, dexamethasone, or 
bortezomib, or until the start of subsequent systemic anti-myeloma treatment, if earlier. Thereafter, 
concomitant therapy given for adverse event/serious adverse event considered related to study 
treatment will be recorded until the end of the study.
In the JNJ-68284528 Treatment Arm (Arm B), the recording period is from the signing of the ICF 
until Day 112 after infusion of JNJ-68284528 regardless if PD occurs prior to Day 112 or 
subsequent anti-myeloma therapy is started prior to Day 112. After Day 112, concomitant therapy 
given for any non-serious adverse event considered related to study treatment or all serious adverse 
events regardless of causality or for delayed adverse events will be recorded until the end of the 
study. Exceptions include medications used to prevent (including vaccines) and treat COVID-19 
and HBV reactivation, which should be reported until 1 year after cilta-cel infusion, regardless of 
severity or causality (Appendix 10.29).
Recorded information will include a description of the type of the drug, dosing regimen, route of 
administration, duration of treatment, and its indication. Medications, including details of previous 
anticancer treatment, should be documented in the appropriate section of the eCRF.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered.
6.5.1.
Recommended Medications
6.5.1.1.
Prophylaxis for Thromboembolism
Pomalidomide has been associated with an increased incidence of deep vein thrombosis and 
pulmonary embolism. Therefore, thromboprophylaxis is strongly recommended for all subjects on 
Arm A and for subjects undergoing bridging therapy on Arm B.
Subjects already on therapeutic anticoagulation may continue their prior anticoagulation regimen. 
All subjects should have their anticoagulation held according to institutional guidelines when 
subjects would be at risk of bleeding due to the combination of significant thrombocytopenia and 
anticoagulation. Once platelet count recovers to an acceptable level per institutional guidelines, 
anticoagulation should be resumed.
Refer to the pomalidomide, prescribing information for recommendations for subjects with prior 
history of thrombosis.
6.5.1.2.
Proton Pump Inhibitor
Prophylactic use of a proton pump inhibitor (PPI) in subjects on Arm A and during bridging 
therapy in subjects on Arm B is recommended. If a contraindication to PPI exists or the subject is 
intolerant to PPIs, a histamine receptor (H2) blocker may be substituted for the PPI.

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6.5.1.3.
Prophylaxis for Infections
Following JNJ-68284528 infusion, prophylaxis with antibacterial (eg, levofloxacin) and antifungal 
medication (eg, fluconazole) is recommended until neutrophil count returns to ≥1 × 109/L. 
Prophylaxis for herpes zoster reactivation is recommended during study treatment (Arm A) or 
during bridging therapy (Arm B). Initiate antiviral prophylaxis to prevent herpes zoster 
reactivation within 1 week after the start of study treatment (Arm A) or the start of bridging therapy 
(Arm B) and continue for at least 6 months following the last dose of study treatment or bridging 
therapy. Acceptable antiviral therapy includes acyclovir, famciclovir, or valacyclovir (per 
institutional standards). Pneumocystis carinii/jirovecii prophylaxis may be considered as per 
institutional guidelines for Arm A and Arm B. Please refer to Appendix 10.29 for guidance on 
prophylaxis (eg, vaccines) and treatment of COVID-19 infection.
6.5.1.4.
Pre-injection Medications for Daratumumab
For all subjects receiving daratumumab (DPd as part of standard therapy for Arm A, or as part of 
bridging therapy for Arm B) pre-injection medications will be administered as described in the 
Schedule of Activities (Table 3). On daratumumab dosing days, subjects will receive the following 
medications 1 to 3 hour prior to daratumumab administration:
!
Dexamethasone 40 mg or 20 mg IV or PO (an equivalent of long acting corticosteroid may 
substitute [Section 10.13]); in this setting dexamethasone will be utilized as the treatment dose 
of corticosteroid for that particular day, as well as the required pre-medication prior to 
daratumumab dosing;
!
Paracetamol (acetaminophen) 650 to 1000 mg IV or PO; and
!
An antihistamine (diphenhydramine 25 to 50 mg IV or PO, or equivalent, but avoid IV use of 
promethazine [Section 10.18]).
!
Leukotriene inhibitor (optional) on C1D1: montelukast 10 mg PO.
If necessary, oral pre- medications may be administered outside of the clinic on the day of the 
administration, provided they are taken within 1 to 3 hours prior to the administration.
6.5.1.5.
Post-Injection Medications for Daratumumab
For subjects with a higher risk of respiratory complications (ie, subjects with COPD who have an 
FEV1 <80% of predicted normal, or subjects with mild asthma), the following post-injection 
medications should be considered:
!
Antihistamine (diphenhydramine or equivalent) on the first and second days after all 
daratumumab administrations
!
Short-acting β2 adrenergic receptor agonist such as salbutamol aerosol
!
Control medications for lung disease (eg, inhaled corticosteroids ±long-acting β2 adrenergic 
receptor agonists for subjects with asthma; long-acting bronchodilators such as tiotropium or 
salmeterol ±inhaled corticosteroids for subjects with COPD)
In addition, these at-risk subjects may be hospitalized for monitoring for up to 2 nights after 
daratumumab administration. If these at-risk subjects are hospitalized, then their FEV1 should be 

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measured before discharge. If these subjects are not hospitalized, then a follow-up telephone call 
should be made to monitor their condition within 48 hours after the first 4 daratumumab 
administrations, or longer if clinically indicated. If the subject has not experienced a significant 
medical event but is hospitalized overnight only for observation, then the hospitalization should 
not be reported as a serious adverse event. Investigators may prescribe bronchodilators, 
antihistamines, and corticosteroids that are deemed necessary to provide adequate supportive care 
in the event a bronchospasm occurs after subjects are released from the hospital/clinic. If an at-risk 
subject experiences no IRRs, then these post-injection medications may be waived after 4 doses at 
the investigator’s discretion.
6.5.1.6.
Prophylaxis for TLS
It is also recommended that subjects at high-risk of TLS, ie, those with a high tumor burden 
(≥60% plasma cell infiltrate on the bone marrow biopsy or aspirate [whichever is higher] or a 
subject with multiple extramedullary disease sites or plasmacytomas) or high LDH be treated 
prophylactically for TLS in accordance with local standards (eg, hydration; diuretics; allopurinol 
300 mg daily or primary or secondary uricosuric agents, as indicated).
Refer to Section 6.1.5.6 for medications subjects should receive prior to JNJ-68284528 infusion. 
6.5.2.
Permitted Medications 
The following are examples of supportive therapies that may be used during the study for subjects 
randomized to either Arm A or Arm B unless otherwise stated:
!
Standard 
supportive 
care 
therapies 
(antiemetics, 
antidiarrheals, 
anticholinergics, 
antispasmodics, antipyretics, antihistamines, analgesics, antibiotics and other antimicrobials, 
histamine receptor [H2] antagonists or PPIs, and other medications intended to treat symptoms 
or signs of disease) and therapies intended to treat CAR-T cell related toxicity (ie, CRS) as 
clinically indicated, according to institutional standards and as deemed necessary by the 
investigator.
!
Bisphosphonates may be administrated as clinically indicated, according to institutional 
standards. The sponsor must be notified promptly in cases where bisphosphonates are given 
for the management of hypercalcemia. 
!
Hematopoietic growth factor support and transfusions (irradiated blood products) are 
permitted to treat symptoms or signs of neutropenia, anemia, or thrombocytopenia according 
to local standards of care. Non-pegylated myeloid growth factors are permitted up to 1 day 
prior to the start of the conditioning regimen (Arm B only) (Section 6.1.5.4).
!
Documented infectious complications should be treated with oral or IV antibiotics or other 
anti-infective agents as considered appropriate by the treating investigator, according to 
standard institutional practice. 
!
Chemotherapy agents used to treat CAR-T cell related toxicity are permitted upon 
consultation with the sponsor (see Section 6.1.6).

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6.5.3.
Prohibited Therapies
The following medications are prohibited during the study for subjects randomized to either 
Arm A or Arm B, as indicated below. The sponsor must be notified in advance (or as soon as
possible thereafter) of any instances in which prohibited therapies are being considered for 
administration (or were administered).
Arm A and Arm B
!
Any chemotherapy, anticancer immunotherapy (other than JNJ-68284528), or experimental 
therapy, except protocol-specified conditioning agents and bridging therapy.
!
Other immunosuppressant agents unless protocol-specified pre- or post-treatment medications 
to treat an adverse event (eg, CRS).
!
Orthopedic surgery or radiotherapy is generally prohibited but may be allowed in the absence 
of disease progression. Prior sponsor notification and approval is required. If necessary, an 
emergency intervention may proceed without prior approval from sponsor. In these cases, the 
sponsor should be notified as soon as is feasible. Such emergency radiotherapy may consist 
of localized radiotherapy for pain control or for stabilization of an extensive bone lesion at 
high risk of pathologic fracture or damage to surrounding tissues.
Arm B
!
After the start of lymphodepletion and prior to Day 112, corticosteroid use should be avoided, 
except for the treatment of CRS or CAR-T cell-related neurotoxicity (ie, ICANS), as described 
in Table 11 and Table 12. Alternative therapies, if feasible, should be given prior to 
corticosteroids.  
!
Vaccination with live, attenuated vaccine in the #6 weeks prior to the start of conditioning 
regimen, and for at least 112 days after infusion of JNJ-68284528.
!
The use of RANK ligand inhibitors such as denosumab is prohibited due to their potential 
impact on immune function.
!
Pegylated myeloid growth factors (ie, pegfilgrastim) are prohibited within the first 112 days 
after infusion with JNJ-68284528.
Therapies to be avoided
!
Nonsteroidal anti-inflammatory agents should be avoided to minimize the risk of exacerbation 
of potential sub-clinical myeloma-related kidney disease. Based on the investigator’s clinical 
judgement, low-dose aspirin may be continued for thromboprophylaxis.
!
The use of IV contrast infusions should be avoided to prevent myeloma-related kidney 
disease. If administration of IV contrast is necessary, then adequate precautions including 
hydration are indicated.
!
For subjects receiving PVd or DPd: avoid concomitant use of pomalidomide with strong 
inhibitors of CYP1A2 (eg, ciprofloxacin, enoxacin, and fluvoxamine). If deemed medically 
necessary, reduce the dose of pomalidomide by 50%.

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6.6.3.
Pomalidomide Dose Modification Guidelines for Non-hematologic 
Toxicities
Pomalidomide interruption or discontinuation should be considered for Grade 2 or 3 skin rash. 
Pomalidomide must be discontinued for angioedema, Grade 4 rash, exfoliative or bullous rash and 
for Stevens-Johnson syndrome/toxic epidermal necrolysis related to pomalidomide and should not 
be resumed following discontinuation for these reactions.
Interstitial lung disease (ILD) and related events, including cases of pneumonitis, have been 
observed with pomalidomide. Careful assessment of subjects with an acute onset or unexplained 
worsening of pulmonary symptoms should be performed to exclude ILD. Pomalidomide should 
be interrupted pending investigation of these symptoms and if ILD is confirmed, appropriate 
treatment should be initiated. Pomalidomide should only be resumed after a thorough evaluation 
of the benefits and the risks.
For subjects whose bortezomib treatment is discontinued, they may continue to receive 
pomalidomide/dexamethasone. For subjects whose pomalidomide/dexamethasone treatment is 
discontinued, bortezomib treatment may be continued.
6.6.4.
Pomalidomide and Daratumumab Dose Modification for Hematologic 
Toxicities
Dose modification of daratumumab SC is not permitted. Dose delay is the primary method for 
managing daratumumab-related toxicities. If a dose is delayed within a cycle, then the next dose 
should be performed at the scheduled timepoint.
Instructions for dose interruptions and reductions for daratumumab and pomalidomide related to 
hematological toxicities are outlined in Table 22.
In case of neutropenia, the physician should consider the use of growth factors.
To initiate a new cycle of DPd, neutrophil count must be ≥1 x 109/L and the platelet count 
≥50 x 109/L.

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Any dose withholding of either daratumumab or pomalidomide for more than 28 days due to 
toxicity will result in permanent discontinuation of the applicable drug. Dose withholdings of more 
than 28 days for other reasons should be discussed with the sponsor.
Subjects missing ≥3 consecutive planned doses of daratumumab for reasons other than toxicity 
should be withdrawn from treatment, unless, upon consultation with the Sponsor and the review 
of safety and efficacy, continuation is agreed upon.
For subjects whose daratumumab treatment is discontinued, they may continue to receive 
pomalidomide/dexamethasone. For subjects whose pomalidomide/dexamethasone treatment is 
discontinued, daratumumab treatment may be continued.
6.6.5.
JNJ-68284528
No dose modification of JNJ-68284528 is allowed.
6.7.
Follow-up for Subsequent Myeloma Therapy and Survival (Arm A and 
Arm B)
Telephone contact will be made to determine the use of subsequent myeloma therapy and survival 
according to the Schedule of Activities (Table 2 to Table 5) until the end of the study or until the 
subject has died, is lost to follow-up, or has withdrawn consent. If the information on subsequent 
myeloma therapy and survival is obtained via telephone contact, written documentation of the 
communication must be available for review in the source documents. If the subject has died, the 
date and cause of death will be collected and documented on the eCRF. Investigators may contact 
the subject to obtain long-term follow up information regarding the subject's safety or survival 
status as noted in the ICF (refer to Informed Consent in Section 10.3), Regulatory, Ethical, and 
Study Oversight Considerations).
6.8.
Intervention After the End of the Study
After the end of the study, subjects in Arm A should return to their primary physician to determine 
further treatment. The sponsor will ensure the subjects on Arm A will have continued access to 
study treatment should this not be available as part of the local standard of care.
Following completion/discontinuation or after study end, subjects in Arm B will enter a separate 
long-term follow-up study (Study 68284528MMY4002) in which assessments for replication 
competent lentivirus (RCL) and delayed AEs, including SPMs (see Section 8.3.1) will be collected 
yearly until 15 years after the last infusion with JNJ-68284528. For subjects diagnosed with a 
SPM, a tumor sample should be collected and DNA, RNA, or protein analysis may be performed 
to investigate the presence of lentiviral elements.

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7.
DISCONTINUATION OF STUDY INTERVENTION AND SUBJECT
DISCONTINUATION/WITHDRAWAL
7.1.
Discontinuation of Study Intervention
7.1.1.
Discontinuation of Study Treatment for Arm A
A subject's study treatment must be discontinued if:
!
The subject withdraws consent to receive study treatment
!
The investigator believes that for safety reasons or tolerability reasons (eg, adverse event) it 
is in the best interest of the subject to discontinue study treatment
!
The subject becomes pregnant. Refer to Section 10.12 Contraceptive and Barrier Guidance 
and Collection of Pregnancy Information.
!
Noncompliance with study treatment administration or protocol requirements
!
Subject received concurrent (non-protocol) anticancer treatment
!
Confirmed PD per IMWG criteria
7.1.2.
Discontinuation of Study Treatment for Arm B
A subject should not receive JNJ-68284528 if:
!
The investigator believes that for safety reasons or tolerability reasons (eg, adverse event) it 
is in the best interest of the subject to discontinue study treatment
!
The subject received concurrent (non-protocol) anticancer treatment (with exception of 
bridging therapy)
!
Subject refuses further study treatment
!
Noncompliance with study treatment or procedure requirements
!
The subject becomes pregnant prior to infusion
!
Signs of active infection or Grade ∀3 non-hematologic toxicity related to cyclophosphamide 
and fludarabine occurs and precludes retreatment with cyclophosphamide and fludarabine 
prior to JNJ-68284528 infusion per Section 6.1.5.4.
The primary reason for treatment discontinuation will be documented in the eCRF and source 
documents. Subjects who are unable to receive PVd or DPd standard therapy for Arm A, or unable 
to be apheresed, or receive bridging therapy, conditioning regimen or JNJ-68284528 infusion for 
Arm B, will be followed until confirmed PD, start of new anti-myeloma therapy, withdrawal of 
consent, or end of the study whichever occurs first. Once PD is confirmed, subsequent disease 
assessment time points are not required. After PD subjects will then be followed for survival status, 
subsequent anti-myeloma therapies, response to subsequent anti-myeloma therapies including the 
date of subsequent progression (PFS2), SPMs for both Arms and other delayed adverse events for 
Arm B until death or the end of the study.

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If a subject on Arm A discontinues study treatment, then an end of treatment visit will be done. 
The post-treatment follow-up assessments should be obtained and scheduled assessments off study 
treatment should be continued. Study treatment assigned to the subject who discontinued study 
intervention may not be assigned to another subject. Additional subjects will not be entered to 
replace subjects who discontinue treatment. If a subject's study treatment is discontinued for any 
reason, this will not result in automatic withdrawal of the subject from the study.
A subject on Arm B who discontinues post-treatment follow-up due to progressive disease will 
continue to be followed for survival status, subsequent anti-myeloma therapies, and delayed AEs 
including SPMs. A subject on Arm B who discontinues post-infusion follow-up due to progressive 
disease prior to Day 112, will continue to be followed for safety (including adverse events/serious 
adverse events) until Day 112, and continued to be followed for survival status, subsequent anti-
myeloma therapies, and delayed AEs including SPMs.
7.2.
Subject Discontinuation/Withdrawal from the Study
A subject will be withdrawn from the study for any of the following reasons:
!
Lost to follow-up
!
Withdrawal of consent
!
The sponsor discontinued the study
The reason(s) for subject withdrawal will be recorded on the eCRF and in source documents. If a 
subject is lost to follow-up, every reasonable effort must be made by the study-site personnel to 
contact the subject and determine the reason for discontinuation/withdrawal. The measures taken 
to follow-up must be documented.
If a subject randomized to Arm A withdraws consent following study treatment dosing, study 
assessments for the End-of-Treatment Visit should be completed prior to withdrawal of consent, 
if feasible. For a subject randomized to Arm B who withdraws consent in the post-infusion period 
(prior to Day 112), the Day 112 assessments should be completed, if withdrawal occurs in the 
post-treatment period, the assessments at PD should be completed prior to withdrawal of consent, 
if feasible.
Withdrawal of Consent
A subject declining to return for scheduled visits or declining to continue study treatment does not 
necessarily constitute withdrawal of consent. Alternate follow-up mechanisms that the subject
agreed to when signing the consent form apply (eg, consult with family members, contacting the 
subject’s other physicians, medical records, database searches, use of locator agencies at study 
completion,) as local regulations permit.
Withdrawal from the Use of Samples in Future Research
The subject may withdraw consent for use of samples for research (refer to Long-Term Retention 
of Samples for Additional Future Research in Section 10.3, Regulatory, Ethical, and Study 
Oversight Considerations). In such a case, samples will be destroyed after they are no longer 

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needed for the clinical study. Details of the sample retention for research are presented in the main 
ICF.
7.3.
Lost to Follow-up
To reduce the chances of a subject being deemed lost to follow-up, prior to randomization attempts 
should be made to obtain contact information from each subject, eg, home, work, and mobile 
telephone numbers and email addresses for both the subject as well as appropriate family members.
A subject will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. A subject cannot be deemed lost to follow-up 
until all reasonable efforts made by the study-site personnel to contact the subject are deemed 
futile. The following actions must be taken if a subject fails to return to the study site for a required 
study visit:
!
The study-site personnel must attempt to contact the subject to reschedule the missed visit as 
soon as possible, to counsel the subject on the importance of maintaining the assigned visit 
schedule, to ascertain whether the subject wishes to or should continue in the study.
!
Before a subject is deemed lost to follow up, the investigator or designee must make every 
reasonable effort to regain contact with the subject (where possible, 3 telephone calls, e-mails, 
fax, and, if necessary, a certified letter to the subject’s last known mailing address, or local 
equivalent methods. Locator agencies may also be used as local regulations permit. These 
contact attempts should be documented in the subject’s medical records.
!
Should the subject continue to be unreachable, they will be considered to have withdrawn 
from the study.
Should a study site close, eg, for operational, financial, or other reasons, and the investigator cannot 
reach the subject to inform them, their contact information will be transferred to another study site.
8.
STUDY ASSESSMENTS AND PROCEDURES
Overview
The Schedule of Activities (Table 2 to Table 5) summarizes the frequency and timing of efficacy, 
PK, immunogenicity, PD, biomarker, safety, PROs,
and medical resource utilization 
measurements applicable to this study.
All planned assessments, including laboratory tests, must be completed and the results reviewed 
prior to the start of study treatment. Treatment decisions will be based on safety assessments 
performed at the local laboratory and disease assessments performed at the central laboratory. 
Local laboratory data may be collected if central laboratory data is not available at a particular 
timepoint, (Section 8.1.6).

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For all other assessments scheduled for the same timepoint, it is recommended that procedures be 
performed in the following sequence: PRO assessments, electrocardiogram (ECG), vital signs, 
blood draw. Blood collections for biomarkers and pharmacokinetic assessments should be kept as 
close to the specified time as possible. Actual dates and times of assessments will be recorded in 
the source documents and the laboratory requisition form. Within 24 hours of JNJ-68284528
infusion in Arm B, if the study treatment is infused peripherally, blood samples must be drawn 
from a vein contralateral to the arm into which JNJ-68284528 is infused. If the study treatment is 
infused via a central vein line, blood samples over the subsequent 24 hours must be drawn from a 
vein in either arm. Repeat or unscheduled blood samples may be taken for safety reasons or for 
technical issues with the samples.
During screening for WOCBP a pregnancy test will be performed 10-14 days prior to the start of 
PVd or DPd but prior to randomization. For WOCBP randomized to Arm A on the PVd standard 
therapy, a pregnancy test will be performed within 24 hours prior to the first dose of PVd, every 
week for the first 4 weeks, every 3 weeks starting from Cycle 3 Day 1, or every 2 weeks for 
WOCBP with irregular menses, and 28 (+7) days following the last dose of pomalidomide. For 
WOCBP randomized to Arm A on the DPd standard therapy, a pregnancy test will be performed 
within 24 hours prior to the first dose of DPd, every week for the first 4 weeks, every 28 days or 
every 14 days for WOCBP with irregular menses, and 28 (+7) days following the last dose of 
pomalidomide (see Schedule of Activities, Table 1, Table 2 and Table 3). 
For WOCBP randomized to Arm B, a pregnancy test will be performed within 72 hours prior to 
apheresis and within 72 hours prior to initiation of conditioning regimen. During the bridging 
therapy, if the pregnancy test done at screening falls out of the required 10-14 days prior to starting 
PVd or DPd, the test will need to be repeated. A pregnancy tests will be performed within 24 hours 
prior to the first dose of PVd or DPd, every week for the first 4 weeks, and 28 (+7) days following 
the last dose of pomalidomide (Schedule of Activities, Table 1, Table 4, Table 5). Additional 
serum or urine pregnancy tests may be performed, as determined necessary by the investigator or 
required by local regulation, to establish the absence of pregnancy at any time during the 
participation in the study.
The approximate blood volume to be collected from each subject in Arm A is up to 384 mL/year. 
For subjects in Arm B the approximate blood volume to be collected from each subject is:
!
Up to 845 mL in Year 1
!
Up to 238 mL in subsequent years.
Sample Collection and Handling
Refer to the Schedule of Activities (Table 2 to Table 5) for the timing and frequency of all sample 
collections. The actual dates and times of sample collection must be recorded in the eCRF or 
laboratory requisition form.
Instructions for the collection, handling, storage, and shipment of samples to the central laboratory 
are found in the central laboratory manual that will be provided. Collection, handling, storage, and 

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shipment of samples must be under the specified, and where applicable, controlled temperature 
conditions as indicated in the laboratory manual. 
Study-Specific Materials
The investigator will be provided with the following supplies:
!
Study protocol
!
Investigator’s Brochure
!
IPPI/SIPPM (now known as CTPPM) (includes apheresis and cell processing instructions)
!
Central laboratory manual
!
Interactive web response system manual
!
PRO instruments and completion guidelines/training materials
!
Electronic data capture (eDC) Manual
!
Sample ICF
!
Subject diaries and instructions/educational materials
Screening Phase
All subjects must sign an ICF prior to the conduct of any study-related procedures. The screening 
phase begins when the first screening assessment is performed. Screening procedures will be 
performed up to 28 days before randomization. If an assessment was performed as part of the 
subject’s routine clinical evaluation and not specifically for this study, it does not need to be 
repeated after signed informed consent has been obtained provided the assessments fulfill the study 
requirements and are performed within the specified timeframe prior to the first dose of study 
treatment. The last result obtained prior to randomization will be used to determine eligibility. 
Subjects who do not meet all inclusion criteria or who meet an exclusion criterion may, at the 
discretion of the investigator, be rescreened once upon the sponsor’s written approval. Subjects 
who are to be rescreened must sign a new informed consent before rescreening. Rescreening and 
subsequent activities must be conducted in accordance with protocol defined time windows.
Randomization
Following the completion of screening assessments, subjects who meet all eligibility criteria will 
be randomized 1:1 to either Arm A or Arm B per the IVRS. 
In both Arm A and Arm B, subjects will be provided a "patient ID card" with pertinent information 
about the study.
Treatment Phase (Arm A)
Subjects should initiate study treatment within 7 days after randomization. Prior to initiation of 
study treatment, review of safety assessments should be completed per Schedule of Activities 
(Table 2 and Table 3). Subjects will be treated in 21-day cycles for the PVd therapy and in 28-day 

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cycles for the DPd therapy until disease progression, unacceptable toxicity, death, withdrawal of 
consent, or end of study.
Apheresis (Arm B only)
Subjects should start apheresis in 3 to 6 days after randomization. Prior to apheresis, review of 
safety assessments should be completed per Schedule of Activities (Table 4). Apheresis should be 
performed according to institutional standards. Instructions for processing and shipping apheresis 
product are provided in the CTPPM.
Treatment Phase-Bridging therapy, Conditioning Regimen, and JNJ-68284528 
Administration (Arm B)
Bridging therapy is administered after apheresis while JNJ-68284528 is being manufactured, prior 
to conditioning regimen. Bridging therapy should be started after apheresis but no more than 
7 days after randomization. The choice of bridging therapy, 1 cycle of PVd or DPd, will be
determined by the investigator prior to screening and will be dependent on the subject’s prior 
exposure to anti-myeloma therapies. A second cycle of bridging therapy may be administered; the 
investigator should contact the sponsor if a second bridging cycle is warranted due to a delay in 
the availability of JNJ-68284528. Cycles beyond Bridging Cycle 1 may be truncated to allow for 
adequate washout and minimize time off therapy.
At the completion of manufacture and quality testing of JNJ-68284528, notification will be sent to 
the clinical site. Prior to dosing with cyclophosphamide and fludarabine, review of safety 
assessments and disease characteristics should be completed per Section 6.1.5.4. Details regarding 
safety monitoring and study visits during this phase are included in the Schedule of Activities
(Table 4 and Table 5). A conditioning regimen of cyclophosphamide 300 mg/m2 and fludarabine 
30 mg/m2 daily for 3 days must be administered prior to administration of JNJ-68284528. The 
dose of fludarabine should be reduced to 24 mg/m2 for subjects with an eGFR of 30 to 
70 mL/min/1.73 m2. Sponsor approval must be obtained to modify the conditioning regimen 
schedule.
Administration of JNJ-68284528 is described in full details in Table 10. Prior to dosing with 
JNJ-68284528, review of safety assessments and disease characteristics should be completed per 
Section 6.1.5.5.
Post-treatment Follow-up Phase (Arm A)
Subjects who discontinue treatment for reasons other than documented disease progression, death 
or withdrawal of consent should continue to be followed for response assessments every 28 days 
as in Schedule of Activities Table 2 and Table 3. If a subject starts new anti-myeloma therapy prior 
to disease progression, every attempt should be made to perform disease evaluations until 
documented disease progression.
Subjects will be followed every 16 weeks, after disease progression for survival status, subsequent 
anti-myeloma therapies, response to subsequent anti-myeloma therapies including the date of 
subsequent progression (PFS2) and SPMs until the end of study. 

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Post-infusion Follow-up Phase and Post-treatment Follow-up Phase (Arm B)
The post-infusion follow-up phase starts after the completion of JNJ-68284528 infusion on Day 1 
and lasts until Day 112. Any subject who receives an infusion of JNJ-68284528 should continue 
all subsequent post-infusion assessments as per the Schedules of Activities (Table 5). During this 
period, subjects will be monitored closely for safety and disease assessments. Subjects will be 
asked to check their temperature at least twice daily (entering 2 temperatures including their 
maximum daily temperature on the provided diary) during the first 28 days after infusion and will 
be instructed to report any fever (≥38°C or ≥100.4°F) to the investigator immediately to initiate 
monitoring for development of CRS. 
At the Investigator’s discretion and patient’s willingness, the subject will be admitted for inpatient 
monitoring from the day of infusion (Day 1) through Day 14 of JNJ-68284528 infusion (with 
potential discharge on Day 10 if there are no CRS, neurotoxicity or other clinically significant 
events), OR will receive JNJ-68284528 infusion as an outpatient in close proximity (within 
30 min) to the hospital, be monitored for outpatient follow-up and then be admitted for the required 
inpatient monitoring from Day 5 to Day 14 after JNJ-68284528 infusion (with potential discharge 
on Day 10 if there are no CRS, neurotoxicity or other clinically significant events) (Table 10, 
Section 10.16, and Section 10.17).
Subjects will be asked to remain within 1 hour of the hospital and in the company of a competent 
adult at all times for 1 additional week after hospital discharge, or until Study Day 21, whichever 
is sooner. 
The post-treatment follow-up phase starts once the post-infusion follow-up is complete (on 
Day 112) and lasts until end of study (defined until approximately 250 deaths have occurred). 
Assessments are to be performed per the Schedule of Activities (Table 5) and include safety and 
disease assessments every 28 days. In the post-treatment follow-up, subjects will continue to be 
monitored for efficacy until confirmed PD, death, or withdrawal of consent. After confirmed PD, 
subjects will be followed for survival, subsequent anti-myeloma therapies, response to subsequent 
anti-myeloma therapies including the date of subsequent progression (PFS2), and SPMs every 
16 weeks until the end of study. The occurrence of SPMs must be reported during the post-infusion 
and post-treatment follow-up and continue until the end of the study. In addition, assessment for 
other delayed AEs will be collected until end of study and will continue to be collected yearly for 
up to 15 years after the JNJ-68284528 administration in a separate long-term follow-up study
(Study 68284528MMY4002). Yearly collection of RCL samples is not required if all assessments 
within the first year are negative. Sites will be notified if a subject’s sample is positive for RCL, 
otherwise RCL is no longer required to be collected after the 12-month visit. PRO assessments 
will continue to be collected in the post-treatment follow-up phase.
If a subject on Arm A or on Arm B has died, the date and cause of death will be collected and 
documented on the eCRF, if or when available. Where allowed by local law, public records may 
be used to document death or to obtain survival status.

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Home Health Care and Telehealth Visits (Arm B)
In exceptional circumstances, home health care and telehealth visits may be implemented 
following the Day 364 visit, following notification from the sponsor and per the clinical judgment 
of the investigator, where feasible and permissible by local policy and regulations. Subjects for 
whom there is no safety concern related to study treatment administration or any pre-existing 
condition(s) may have home health care and telehealth (conducted via phone or video conference) 
visits.
Study procedures such as ECOG assessment, vital signs, adverse event and concomitant 
medication reporting may be performed with home health care and telehealth visits. Protocol-
specified laboratory assessments for efficacy and safety may be collected during home health care 
visits or at a local laboratory. At a minimum, subjects must return to the study site for bone marrow 
aspirate/biopsy and PRO completion as outlined in the Schedule of Activities. At these visits, a 
central disease evaluation sample should be collected.
If local laboratories are used, it is important to ensure appropriate documentation of laboratory 
reference ranges. Source documentation and the appropriate eCRFs must be completed.
8.1.
Efficacy Assessments
Disease evaluations must be performed as specified in the Schedule of Activities (Table 2 to
Table 5). Disease evaluations will be performed by a central laboratory (additional samples may 
be collected for analysis by the local laboratory) until PD, death, withdrawal of consent, or end of 
the study.
Local laboratory assessments may be used under specified circumstances 
(Section 8.1.6). Response assessments will be based on IMWG response criteria (Section 10.7). 
The sponsor will use a validated computer algorithm to analyze response to treatment.
Disease progression must be confirmed by repeating central laboratory testing (See Section 8.1.6
for exceptions) at any time before the institution of any new therapy. The investigational sites are 
requested to notify the sponsor within 1 working day if a subject on either Arm A or Arm B has 
been diagnosed with disease progression (that is also confirmed with a consecutive assessment if 
based on M-protein/serum free light chain [FLC] levels) and provide documentation of disease 
progression. The sponsor’s medical monitor will review the data provided to confirm that the 
IMWG criteria for PD have been met (see Section 10.7). Study treatment discontinuation (Arm A) 
or discontinuation from post-treatment follow-up (Arm B) and start of subsequent anti-myeloma 
therapy should occur only after sponsor confirmation of PD.
8.1.1.
Myeloma Protein Measurements in Serum and Urine
Blood and 24-hour urine samples for M-protein measurements will be sent to and analyzed by a 
central laboratory until the development of confirmed disease progression. Local laboratory 
assessments may be used under specified circumstances (Section 8.1.6). Assessments, listed 
below, will be performed as specified in the Schedule of Activities (Table 2 to Table 5).
!
Serum quantitative immunoglobulin 
!
Serum protein electrophoresis (SPEP)

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!
Serum immunofixation electrophoresis 
!
Serum FLC assay (for subject in suspected CR/sCR and every disease assessment for subjects 
with serum FLC only disease)
!
24-hour urine M-protein quantitation by electrophoresis (UPEP)
!
Urine immunofixation electrophoresis 
Disease progression based on one of the laboratory tests alone must be confirmed by at least 
1 repeat investigation. Disease evaluations will continue beyond relapse from CR until disease 
progression is confirmed. Serum and urine immunofixation and serum free light chain assays will 
be performed at screening, at C1D1 (Arm A), or prior to apheresis (Arm B) and thereafter when a
CR is suspected (when serum or 24-hour urine M-protein electrophoresis [by SPEP or UPEP] is 0 
or non-quantifiable). For subjects with light chain MM, serum and urine immunofixation tests will 
be performed routinely as per the Schedule of Activities (Table 2 to Table 5).
Daratumumab-specific Immunofixation Electrophoresis (DSIFE) for Subjects Treated with 
Daratumumab (Arm A on the DPd Standard Therapy or Arm B on DPd as Bridging 
Therapy)
Daratumumab may be detected on SPEP and SIFE assays used for monitoring disease monoclonal
immunoglobulins (M-protein). This can lead to false positive SPEP and SIFE assay results for 
subjects with IgG kappa myeloma protein and affect assessments of responses based on modified 
IMWG criteria.
Therefore, a DSIFE will be performed when daratumumab interference is suspected based on 
SPEP and SIFE results. For subjects in Arm A, DSIFE is not required once CR/sCR is confirmed. 
For subjects in Arm B, DSIFE is not required after bridging therapy and prior to conditioning 
regimen. This reflex assay relies on the use of a daratumumab specific murine anti-idiotype 
antibody that binds and shifts daratumumab’s migration pattern during electrophoresis, thus 
distinguishing daratumumab from the endogenous myeloma M protein.27 The DSIFE will be 
performed at a central laboratory to confirm a VGPR or better in subjects with IgG kappa myeloma 
when daratumumab interference is suspected based on SPEP and SIFE results.
8.1.2.
Imaging
Imaging must be performed at screening and thereafter as clinically indicated. Imaging will be 
interpreted locally. Any of the following are acceptable, however, the same modality should be 
used for screening and if indicated to evaluate for possible PD:
!
A skeletal survey (including skull, entire vertebral column, pelvis, chest, humeri, femora, and 
any other bones for which the investigator suspects involvement by disease).
!
Whole body MRI
!
Low-dose whole body CT
!
Positron emission tomography (PET)/CT with diagnostic CT component. If a CT scan is used,
it must be of diagnostic quality.

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Following study treatment, and before disease progression is confirmed, X-rays or CT scans should 
be performed locally, whenever clinically indicated based on symptoms, to document response or 
progression. If a subject presents with disease progression manifested by symptoms of pain due to 
bone changes, then disease progression may be documented by skeletal survey or other 
radiographs, depending on the symptoms that the subject experiences. If the diagnosis of disease 
progression is obvious by radiographic investigations, then no repeat confirmatory X-rays are 
necessary. If changes are equivocal, then a repeat X-ray is needed in 1 to 3 weeks.
The modality used for imaging must be indicated on the eCRF. Imaging reports must be made 
available to sponsor for central team review upon request.
8.1.3.
Documentation of Soft Tissue Plasmacytomas
Sites of known soft tissue plasmacytomas must be documented during screening. Clinical 
examination or MRI may be used to document soft tissue plasmacytomas. CT scan evaluations are 
an acceptable alternative if there is no contraindication to the use of IV contrast. Positron emission 
tomography scan or ultrasound tests are not acceptable to document the size of soft tissue 
plasmacytomas. However, PET/CT scans can be used to document soft tissue plasmacytomas if 
the CT component of the PET/CT scan is of sufficient diagnostic quality. If PET/CT identifies soft 
tissue disease and CT is not of diagnostic quality, additional diagnostic quality cross-sectional 
imaging should be performed to obtain bi-dimensional measurements.
Soft tissue plasmacytomas should be assessed for all subjects with a history of plasmacytomas, by 
clinical examination or radiologic imaging. Assessment of measurable sites of extramedullary 
disease will be performed, measured, and evaluated locally every 4 weeks in subjects where 
plasmacytoma is measurable on physical examination. Assessments will continue every 4 weeks
or every 12 weeks until development of confirmed CR or confirmed disease progression as long 
as the soft tissue plasmacytoma remains measurable on physical or radiological examination. If 
assessment can only be performed radiologically, then evaluation of soft tissue plasmacytomas 
should be done every 12 weeks. The methodology used for evaluation of each disease site should 
be consistent across all visits. Irradiated or excised lesions will be considered not measurable and 
will be monitored only for disease progression. 
To qualify for VGPR or PR/minimal response, the sum of products of the perpendicular diameters 
of the existing soft tissue plasmacytomas must have decreased by over 90% or at least 50%, 
respectively, and new plasmacytomas must not have developed (see the disease response criteria 
in Section 10.7). To qualify for disease progression, either the sum of products of the perpendicular 
diameters of the existing soft tissue plasmacytomas must have increased by at least 50%, or the 
longest diameter of previous lesion >1 cm in short axis must have increased at least 50%, or a new 
plasmacytoma must have developed. When not all existing soft tissue plasmacytomas are reported, 
but the sum of products of the perpendicular diameters of the reported plasmacytomas have 
increased by at least 50%, then the criterion for disease progression is met.
The modality used to document soft tissue plasmacytomas must be indicated on the eCRF. Imaging 
reports must be made available to the sponsor for central team review upon request.

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8.1.4.
Bone Marrow Examination
Bone marrow aspirate or biopsy (biopsy alone is acceptable if aspirate is not possible) will be 
performed for clinical assessments and biomarker evaluations. Clinical staging (morphology and 
immunohistochemistry or immunofluorescence or flow cytometry) should be done by a local 
laboratory; cytogenetics will be done at a central laboratory. If cytogenetic results are not available 
by central laboratory, local laboratory data, if available, may be entered into the eCRF. Bone 
marrow aspirate and biopsy will also be performed to confirm CR and sCR (both Arms) and at PD
(Arm B only). For subjects in Arm B, a portion of the bone marrow aspirate at each bone marrow 
aspiration should be sent to the central laboratory for flow cytometry, CyTOF, and to monitor 
BCMA, checkpoint ligand expression in CD138-positive MM cells, and checkpoint expression on
T cells. Additionally, subjects on Arm B will have bone marrow aspirate performed at 6 months 
post-JNJ-68284528 infusion if not performed within the past 3 months. In the event FISH analysis 
does not yield diagnostic results (either centrally or locally), archived bone marrow aspirate or 
bone marrow clot sample may be collected for FISH analysis.
8.1.5.
Minimal Residual Disease Evaluations
Bone marrow aspirates will be collected to monitor MRD to define the myeloma clones as 
specified in the Schedule of Activities (Table 2 to Table 5). MRD negativity is being evaluated in 
the field as a potential surrogate for PFS and OS. MRD will be evaluated using NGS on bone 
marrow aspirate DNA. In the event fresh bone marrow aspirate will not be collected at Screening, 
or if the fresh aspirate does not yield a usable clone, non-decalcified diagnostic tissue (bone
marrow aspirate slides or formalin-fixed paraffin embedded tissue) should be collected for 
calibration of myeloma cells to facilitate the assessment of the secondary MRD endpoints by NGS.
Bone marrow aspirate should be sent to central laboratory for MRD evaluation as specified in the 
Schedule of Activities (Table 3, Table 4, Table 5). If a clone for MRD detection cannot be 
identified based on central or local material, the sponsor will notify the investigator and the subject 
does not need to continue with bone marrows specifically aimed at MRD detection.
8.1.6.
Local Laboratory Assessments
All efforts should be made to collect efficacy data centrally. However, local laboratory data may 
be collected if central laboratory data is not available at a particular timepoint. If both a central 
and a local lab is taken on the same day, the central lab takes precedent. Documentation of the 
local laboratory data should be sent to the Principal Investigator and filed in the medical record. It 
is the Principal Investigator’s responsibility to ascertain that these results are reviewed and entered 
into the subject’s medical record and the eCRF.
8.2.
Safety Assessments 
Safety will be measured by adverse events, laboratory test results, vital sign measurements, 
physical examination findings (including neurologic examination), assessments of cardiac 
function, ICE score (Arm B only), handwriting assessments (Arm B only), and assessment of
ECOG performance status grade according to the time points provided in the Schedule of 
Activities. Clinically relevant changes occurring during the study must be recorded on the adverse 
event section of the eCRF. Any clinically significant abnormalities persisting at the end of the 

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study/early withdrawal will be followed by the investigator until resolution or until a clinically 
stable condition is reached. Safety monitoring assessments may be performed more frequently, if 
clinically indicated.
Adverse events will be reported and followed by the investigator as specified in Section 8.3, 
Adverse Events and Serious Adverse Events and Section 10.4, Adverse Events: Definitions and
Procedures for Recording, Evaluating, Follow-Up, and Reporting.
8.2.1.
Physical Examinations
At screening, a physical examination will be performed and will include, at a minimum, subject’s 
height, general appearance, examination of the skin, ears, nose, throat, lungs, heart, abdomen, 
extremities, musculoskeletal system, neurologic system, and lymphatic system. Thereafter, all 
other exams will be symptom-directed physical examination to be conducted per the Schedule of 
Activities (Table 2 to Table 5) and additional examinations as clinically indicated. Abnormalities 
will be recorded in the appropriate section of the eCRF. In Arm B, weight will be measured prior 
to apheresis and prior to infusion of JNJ-68284528 (see the Schedule of Activities, Table 4 and
Table 5).
8.2.2.
Vital Signs
Temperature, pulse/heart rate, respiratory rate, blood pressure and oxygen saturation will be 
assessed as specified in the Schedule of Activities. Blood pressure and pulse/heart rate 
measurements should be preceded by at least 5 minutes of rest in a quiet setting without distractions 
(eg, television, cell phones). 
Subjects in Arm B will be asked to check their temperature at least twice daily (entering 
2 temperatures including their maximum daily temperature on the provided diary) for the first 
28 days following JNJ-68284528 infusion. Subjects will be instructed to report any fever (≥38°C 
or ≥100.4°F) to the investigator immediately to initiate monitoring for development of CRS.
8.2.3.
Electrocardiograms
Twelve-lead ECGs will be performed at screening and thereafter as clinically indicated.
During the collection of ECGs, subjects should be in a quiet setting without distractions 
(eg, television, cell phones). Subjects should rest in a supine position for at least 5 minutes before 
ECG collection and should refrain from talking or moving arms or legs.
Additional cardiovascular assessments should be performed as clinically appropriate to ensure 
subject safety. The clinical investigator will review the results, including ECG morphology, for 
immediate management. Abnormalities noted at screening should be included in the medical 
history.
8.2.4.
Clinical Safety Laboratory Assessments
Blood samples for serum chemistry and hematology, including CD4/CD8 lymphocyte panel for 
Arm B, will be collected as noted in Section 10.2, Clinical Laboratory Tests. The laboratory tests 

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will be performed by the local laboratory. The investigator must review the laboratory results, 
document this review, and record any clinically relevant changes occurring during the study in the 
adverse event section of the eCRF. Subjects with Grade 3 or higher toxicity or unresolved adverse 
events will continue to be assessed until recovery to Grade #1 or baseline, the event is deemed 
irreversible, the end of the study, or a maximum of 6 months, whichever occurs first.
Laboratory certificates or accreditation and normal ranges of the laboratory facility at the site must 
be submitted to the sponsor before the enrollment of any subject at the site. If the subject has the 
laboratory assessments conducted at a laboratory facility other than the one associated with the 
investigational site, the investigator must submit to the sponsor laboratory certificates or 
accreditation and normal ranges for that facility as well. The laboratory reports must be filed with 
the source documents. Disease-related laboratory evaluations are detailed in Section 8.1. 
8.2.5.
Eastern Cooperative Oncology Group Performance Status
Eastern Cooperative Oncology Group performance status will be used to evaluate the effect of the 
disease status on the activities of daily living (Section 10.10). 
8.2.6.
Transthoracic Echocardiogram or MUGA Scan
Assessment of cardiac function using either transthoracic echocardiogram (TTE) or MUGA scan 
is required. At a minimum, this will include assessment of left ventricular ejection fraction reported 
as a percentage. This value should be recorded in the eCRF. 
8.2.7.
Neurologic Examination
Magnetic resonance imaging (MRI) at screening or neurology consultation should be considered 
if pre-existing CNS disease is suspected. For subjects with prior pertinent neurologic disease 
(eg, stroke, encephalitis) consider baseline MRI of brain and an EEG. For subjects randomized to 
Arm B, at the first sign of neurotoxicity, neurology consultation and evaluation should be 
considered. CAR-T cell-related neurotoxicity (eg, ICANS) should be graded using American 
Society for Transplantation and Cellular Therapy (ASTCT) consensus grading. Other neurological 
adverse events which could not be graded by ASTCT grading should be graded based on CTCAE 
version 5.0. Findings from neurological evaluation and testing that support CAR-T cell-related 
neurotoxicity (eg, ICANS) should be reported in the eCRF. Submission of neuroimaging scans 
may also be requested for sponsor review.
Immune-effector Cell-associated Encephalopathy (ICE) Tool Scores (Arm B)
The ICE test was developed to provide objectivity for the grading of multiple overlapping 
encephalopathy terms currently included on the approved CAR-T products (Section 10.15).24 The 
ICE tool will be collected as noted in the Schedule of Activities (Table 5) to guide management 
throughout the study. It will also be used to grade the severity of ICANS (Section 10.24). All ICE-
Tool scores must be reported in the eCRF.

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Handwriting Assessment
Qualitative changes in handwriting since baseline are being explored by the sponsor as a potential 
early clinical predictive marker for neurotoxicity. Currently no standardized CTCAE toxicity 
gradings are available in the NCI-CTCAE v5.0. for these type of changes in handwriting. 
Therefore, the sponsor has developed a handwriting assessment criterion to assess subjects for 
occurrence of the following types of changes in handwriting: micrographia, dysgraphia, or 
agraphia, as potential early indicators for neurotoxicity (See Section 10.27).
Handwriting assessments will be collected on a writing log according to the Schedule of Activities 
(Table 5) and as instructed by the sponsor. Subjects unable to write at baseline are excused from 
this assessment during study. The sponsor’s medical monitor should immediately be notified when 
changes in handwriting are detected. This will prompt discussion about additional assessments to 
further evaluate for other neurotoxicity symptoms, further workup, as well as the potential 
initiation of interventions. All cases of handwriting abnormalities (ie, micrographia, dysgraphia, 
or agraphia) must be reported as an adverse event in the eCRF. Should a subject experience a 
serious CAR-T associated neurotoxicity (either ICANS or other neurotoxicity), then a copy of the 
handwriting assessment log should be submitted with the serious adverse event report.
8.3.
Adverse Events and Serious Adverse Events
Timely, accurate, and complete reporting and analysis of safety information from clinical studies 
are crucial for the protection of subjects, investigators, and the sponsor, and are mandated by 
regulatory agencies worldwide. The sponsor has established Standard Operating Procedures in 
conformity with regulatory requirements worldwide to ensure appropriate reporting of safety 
information; all clinical studies conducted by the sponsor or its affiliates will be conducted in 
accordance with those procedures.
Adverse events will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or 
the subject’s legally acceptable representative) for the duration of the study.
Anticipated events will be recorded and reported as described in Section 8.3.6.
For further details on adverse events and serious adverse events (Definitions and Classifications; 
Attribution Definitions; Severity Criteria; Special Reporting Situations; Procedures) as well as 
product quality complaints, refer to Section 10.4, Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-Up, and Reporting.
8.3.1.
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information
All Adverse Events
All adverse events (with the exception of delayed AEs [see below], and HBV reactivation and 
COVID-19 infection) and special reporting situations, whether serious or non-serious, will be 
reported as follows:

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!
Arm A: from the time a signed and dated ICF is obtained until 30 days after the last dose of 
study treatment (daratumumab, pomalidomide, dexamethasone, or bortezomib) or until the 
start of subsequent anti-myeloma therapy, if earlier. Beyond this adverse event reporting 
period, only adverse events that are considered related to study drug need to be reported until 
the end of the study.
!
Arm B: from the time a signed and dated ICF is obtained until 30 days after the last dose of 
bridging therapy (daratumumab, pomalidomide, dexamethasone, or bortezomib) or until 
Day 112 post-infusion of JNJ-68284528 (whichever is later) and regardless if PD occurs
during bridging therapy or prior to Day 112 or subsequent anti-myeloma therapy is started 
prior to Day 112. Beyond this adverse event reporting period, non-serious AEs that are 
considered related to a study drug need to be reported until the end of the study except as 
defined for delayed AEs below. Events of HBV reactivations and COVID-19 infection will 
be reported during the first-year post-infusion of JNJ-68284528. 
See Section 10.30, Appendix 30 for additional guidance on AE reporting.
Adverse events and special reporting situations, whether serious or non-serious, will be collected 
for subjects in Arm A who are unable to receive PVd or DPd standard therapy (Arm A), or unable 
to be apheresed, or receive bridging therapy, conditioning regimen, or JNJ-68284528 infusion 
(Arm B) until PD or until the start of anti-myeloma therapy, whichever is earlier.
An assessment of severity grade will be made by the investigator according to the NCI-CTCAE 
Version 5.0, except for CRS and CAR-T cell-related neurotoxicity (eg, ICANS). Cytokine release 
syndrome should be evaluated according to the ASTCT consensus grading (Section 10.25).24
CAR-T cell-related neurotoxicity (eg, ICANS) should be graded using the ASTCT consensus 
grading (Section 10.24). In addition to capturing ICANS and CRS adverse events (graded by 
ASTCT consensus grading), all individual symptoms of CRS (eg, fever, hypotension) and ICANS 
(eg, depressed level of consciousness, seizures) must be captured as individual adverse events and 
graded by CTCAE criteria. Neurotoxicity that is not temporarily associated with CRS, or any other 
neurologic adverse events that do not qualify as ICANS, will be graded by CTCAE criteria. Events 
of neurotoxicity or exacerbation of existing neurologic adverse events will be reported until the 
end of study.
Changes in handwriting (ie, micrographia, dysgraphia, or agraphia) should be graded using the 
criteria outlined in Section 10.27 and reported as an adverse event in the eCRF. Should a subject 
experience a serious CAR-T associated neurotoxicity (either ICANS or other neurotoxicity), then 
a copy of the handwriting assessment log should be submitted with the serious adverse event
report.
Adverse Events of Special Interest
For Arms A and B, second primary malignancies are AEs of special interest and will be followed 
as part of standard safety monitoring activities by the sponsor, regardless of severity or causality 
from the time of randomization to the end of study. For the purpose of reporting, this includes both 
new primary malignancies and recurrence of pre-existing malignancies with the exception of MM 
(which should be reported as PD). 

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In addition, for Arm B, CRS, and neurotoxicity (including CAR-T cell-related neurotoxicity 
[ie, ICANS] and other neurotoxicities) are also AEs of special interest and will be followed as part 
of standard safety monitoring activities by the sponsor, from the time of JNJ-68284528 infusion 
and for the duration of study, regardless of severity or causality. These events will require 
enhanced data collection in the eCRF, be reported to the sponsor in a timely manner irrespective 
of seriousness, and be followed until recovery or until there is no further improvements.
In addition, for Arm B, the following must be reported to the sponsor using the Serious Adverse 
Event process within 24 hours of awareness of the event beginning from Day 1 cilta-cel infusion 
and for the duration of the study, irrespective of seriousness (eg, serious or nonserious AEs) or 
causality:
o
≥Grade 3 CRS
o
≥Grade 3 neurotoxicity
o
Any grade movement and neurocognitive toxicity (ie, parkinsonism)
o
Any grade SPMs (including recurrence of pre-existing malignancies)
Adverse events of special interest meeting the above criteria that are considered to be nonserious 
by the investigator are to be indicated as such on the SAE form and in the eDC tool. All AEs of 
special interest of any grade should be followed until recovery or until there is no further 
improvement.
Delayed Adverse Events
For Arm B, the following delayed AEs will be collected beginning from Day 1 JNJ-68284528
infusion (with the exception of malignancies which will be collected beginning from time of 
randomization) and for the duration of study regardless of causality and subsequently will be 
collected yearly in a long-term follow-up study for up to 15 years post-infusion of cilta-cel:
!
All grade SPMs (defined as new primary malignancies or recurrence of pre-existing 
malignancy with the exception of MM, which should be reported as PD), must be reported to 
the sponsor within 24 hours of awareness of the event for the duration of the study, irrespective 
of seriousness or causality. In the event of malignancy, a tumor sample should be collected, 
and vector integration site analysis may be performed for possible insertional mutagenesis.
!
New incidence or exacerbation of a pre-existing neurologic disorder (all grades). Grade 3 or 
higher neurotoxicity and any grade movement and neurocognitive toxicity (ie, parkinsonism) 
must be reported to the sponsor within 24 hours of awareness of the event for the duration of 
the study, irrespective of seriousness or causality.
!
New incidence or exacerbation of a pre-existing rheumatologic or other autoimmune disorder 
(all grades)
!
New incidence of Grade ≥3 hematologic disorder 
!
New incidence of Grade ≥3 infection 

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Serious Adverse Events
In Arm A, serious adverse events (regardless of causality), including those spontaneously reported 
to the investigator within 30 days after the last dose of study treatment (daratumumab, 
pomalidomide, dexamethasone, or bortezomib) or until the start of subsequent anti-myeloma 
therapy, if earlier must be reported. Beyond this reporting period, only SAEs that are considered 
related to study drugs need to be reported. In Arm B, SAEs (regardless of causality and regardless 
of PD or subsequent anti-myeloma therapy) must be reported for the duration of the study and 
subsequently will be collected yearly in a long-term follow-up study (Study 68284528MMY4002)
for up to 15 years post-infusion of cilta-cel. The sponsor will evaluate any safety information that 
is spontaneously reported by an investigator beyond the time frame specified in the protocol.
All serious adverse events occurring during the study must be reported to the appropriate sponsor 
contact person by study-site personnel within 24 hours of their knowledge of the event.
Events that require an escalation of care when the subject is already hospitalized should be 
recorded as a serious adverse event. Examples of such events include movement from routine care 
in the hospital to the ICU or if that event resulted in a prolongation of the existing planned 
hospitalization.
Information regarding serious adverse events will be transmitted to the sponsor using the Serious
Adverse Event Form and Safety Report Form of the eCRF, which must be completed and reviewed 
by a physician from the study site and transmitted to the sponsor within 24 hours. The initial and 
follow-up reports of a serious adverse event should be transmitted electronically or by facsimile 
(fax).
8.3.2.
Follow-up of Adverse Events and Serious Adverse Events
Adverse events, including pregnancy, will be followed by the investigator as specified in 
Section 10.4, Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-up, 
and Reporting.
8.3.3.
Pregnancy
All initial reports of pregnancy in female subjects or partners of male subjects must be reported to 
the sponsor by the study-site personnel within 24 hours of their knowledge of the event using the 
appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, spontaneous 
abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are considered serious 
adverse events and must be reported using the Serious Adverse Event Form. Any subject who 
becomes pregnant during the study must discontinue further study treatment. Because the effect of 
the study treatment on sperm is unknown, pregnancies in partners of male subjects included in the 
study will be reported as noted above. Follow-up information regarding the outcome of the
pregnancy and any postnatal sequelae in the infant will be required.
Because of the embryo-fetal risk of pomalidomide, all subjects treated with PVd or DPd must be 
enrolled in the pomalidomide pregnancy prevention program applicable in their region. 
Investigators should comply with the Global Pomalidomide Pregnancy Prevention Plan or with 

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the respective country-specific Pomalyst®/Imnovid® (pomalidomide) Risk Minimization Program 
(ie, Pregnancy prevention program) as implemented in the post-marketing setting and ensure that 
all subjects adhere to these programs. When no Pomalyst/Imnovid (pomalidomide) Risk 
Minimization Program exists, subjects must adhere to the Global Pomalidomide Pregnancy 
Prevention Plan.
8.3.4.
Disease-Related Events and Disease-Related Outcomes not 
Qualifying as Adverse Events or Serious Adverse Events
Disease progression should not be recorded as an adverse event or serious adverse event term; 
instead, signs and symptoms of clinical sequelae resulting from disease progression/lack of 
efficacy will be reported if they fulfill the serious adverse event definition (refer to Adverse Event 
Definitions and Classifications in Section 10.4, Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting). Expected PD should not be considered an 
adverse event (or serious adverse event). However, if determined by the investigator to be more 
likely related to the study treatment than the underlying disease, the clinical signs or symptoms of 
progression and the possibility that the study treatment is enhancing disease progression, should 
be reported per the usual reporting requirements.
All deaths not related to PD occurring at any time of the study after receiving JNJ-68284528
administration (Arm B) should be reported to the sponsor following expedited reporting
procedures (see Section 10.4).
8.3.5.
Regulatory Reporting Requirements for Serious Adverse Events
The sponsor assumes responsibility for appropriate reporting of adverse events to the regulatory 
authorities. The sponsor will also report to the investigator (and the head of the investigational 
institute where required) all suspected unexpected serious adverse reactions (SUSARs). The 
investigator (or sponsor where required) must report SUSARs to the appropriate Independent 
Ethics Committee/Institutional Review Board (IEC/IRB) that approved the protocol unless 
otherwise required and documented by the IEC/IRB. 
8.3.6.
Anticipated Events
An anticipated event is an AE (serious or non-serious) that commonly occurs as a consequence of 
the underlying disease or condition under investigation (ie, disease-related) or background 
regimen. For the purposes of this study the following serious adverse events will be considered 
anticipated events:
!
Hypercalcemia
!
Hyperuricemia
!
Bleeding
!
Renal failure and insufficiency
!
Bone diseases

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These anticipated events will be periodically analyzed in aggregate by the sponsor during study 
conduct. The sponsor will prepare a safety report in narrative format if the aggregate analysis 
indicates that the anticipated event occurs more frequently in the treatment group than in the 
control group and the sponsor concludes there is a reasonable possibility that the drug under 
investigation caused the anticipated event.
The plan for monitoring and analyzing the anticipated events is specified in a separate Anticipated 
Events Safety Monitoring Plan. The assessment of causality will be made by the sponsor’s 
unblinded safety assessment committee.
The sponsor assumes responsibility for appropriate reporting of the listed anticipated events 
according to the requirements of the countries in which the studies are conducted.
Note: Some countries require reporting of all AEs to the health authorities and do not identify 
anticipated events for safety reporting purposes.
8.4.
Treatment of Overdose
Refer to the local product prescribing information for bortezomib, pomalidomide, or 
dexamethasone and to the daratumumab Investigator’s Brochure regarding overdose. JNJ-
68284528 will be manufactured, formulated and provided by sponsor individually. Product 
received should be administered in a single infusion. In the event the manufactured product 
exceeds the protocol-defined maximum dose, the product will be evaluated per company 
exceptional release or similar procedures (see Section 6.1.5.3) prior to shipment to clinical site.
There is no risk for overdose of JNJ-68284528.
8.5.
Pharmacokinetics (Arm B Only)
Venous blood samples will be used to evaluate the PK of JNJ-68284528. Samples collected for 
PK may additionally be used to evaluate safety or efficacy aspects that address concerns arising 
during or after the study period. Genetic analyses will not be performed on these serum samples. 
Subject confidentiality will be maintained.
8.5.1.
Evaluations
Venous blood samples will be collected for measurement of JNJ-68284528-positive cellular 
concentration and transgene levels of JNJ-68284528 as specified in the Schedule of Activities 
(Table 4 and Table 5). Samples will also be collected at the time of onset of suspected CRS or 
JNJ-68284528 cell-related neurotoxicity (ie, ICANS) regardless of causality (as specified in
Table 5).
Bone marrow samples will be collected for measurement of cellular concentrations of 
JNJ-68284528 (as specified in Table 5). 
Serum samples will be collected for exploratory evaluations of soluble circulating BCMA. The
data may be used for mechanistic pharmacokinetic/pharmacodynamic modeling.

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The exact dates and times of sampling must be recorded on the laboratory requisition form. Refer 
to the Laboratory Manual for sample collection requirements. Collected samples must be stored 
under specified controlled conditions for the temperatures indicated in the Laboratory Manual.
8.5.2.
Analytical Procedures
Post-dose blood samples will be analyzed to determine CAR-T positive cellular concentration and 
transgene levels of JNJ-68284528 based on the Schedule of Activities (Table 5) using a specific 
and sensitive assay methods that are validated by or under the supervision of the sponsor.
8.5.3.
Pharmacokinetic Parameters and Evaluations
Pharmacokinetic parameters will be estimated for individuals, and descriptive statistics will be 
calculated. Correlation of maximum peripheral blood concentration (Cmax) and area under the 
peripheral
blood concentration-time curve
(AUC)
with dose may also be explored. 
Pharmacokinetic parameters include, but are not limited to, AUC from time 0 to infinity (AUCinf), 
AUC from time 0 to t (AUC[0-t]), Cmax, half-life, and time to reach maximum peripheral blood 
concentration (Tmax) parameters will be calculated if sufficient data are available for estimation.
8.6.
Pharmacodynamics
Pharmacodynamic assessments will only be conducted in subjects who received JNJ-68284528 
and are described in Section 8.9, Biomarkers.
Pharmacokinetic/pharmacodynamic modeling will be explored to understand and characterize the 
dose-response relationship.
8.7.
Pharmacokinetic/Pharmacodynamic Evaluations
Pharmacokinetic/pharmacodynamics modeling may be performed, including exploring the 
relationship between CAR-T count/transgene level and endpoints of clinical efficacy and safety. 
If these analyses are performed, then the details and results will be presented in a separate report.
8.8.
Genetics
Pharmacogenomics are not evaluated in this study.
8.9.
Biomarkers
Biomarker assessments will focus on several objectives: 1) evaluate apheresis and infused CAR-T 
cell subsets and activation markers including, but not limited to, CD4+, CD8+, CD25+, central 
memory, effector memory cells; 2) serum or plasma proteomic profiling of cytokines (such as 
IL-6, IL-15, and IL-10) and other immune related proteins; 3) immunophenotyping of biomarkers 
of response/resistance on myeloma cells (such as BCMA and PD-L1); and 4) immunophenotyping 
of immune cells subsets such as CD4+ and CD8+ T cells, regulatory T cells, B and NK cells. 
Additional biomarker samples may be collected to help understand an unexplained adverse event
including but not limited to serum or PBMCs from whole blood. Additional samples for cytokines 
will be collected as clinically indicated (Schedule of Activates Table 5).

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To monitor if RCL is generated from cilta-cel, whole blood from subjects in Arm B will be 
evaluated using a qPCR assay against the lentiviral vesicular stomatitis virus-G gene. If all post-
infusion samples for an individual subject are negative for RCL during the first year after 
treatment, no additional samples will be collected and RCL assessments will be terminated. Yearly 
review of medical history will generally be sufficient for the subject. Sites will be notified if a 
subject’s sample is positive for RCL, otherwise RCL is no longer required to be collected after the 
12-month visit. If any post-infusion samples are positive, further RCL analysis and more extensive 
subject follow-up should be undertaken. Additional event triggered testing for RCL may be 
conducted as clinically indicated, as specified in the Schedule of Activities (SoA).
Peripheral blood mononuclear cells will be retained for exploratory analysis of the immune system 
which may include retroviral insertion analysis, T-cell receptor analysis (both clonality and/or 
diversity of T-cell receptor), functional in vitro assays, or other. 
Biomarker analyses are dependent upon the availability of appropriate biomarker assays and may 
be deferred or not performed if during or at the end of the study it becomes clear that the analysis 
will have no scientific value, or if there are not enough samples or not enough responders to allow 
for adequate biomarker evaluation. In the event the study is terminated early or shows poor clinical 
efficacy, completion of biomarker assessments is based on the intended utility of the data.
Based on emerging scientific evidence, the sponsor may request additional material including, but 
not limited to, previously collected bone marrow samples, whole blood, bone marrow aspirate or 
biopsy, or other tissue sample during or after study completion for a retrospective analysis. For 
subjects in Arm B diagnosed with a SPM, a tumor sample should be collected (See 
Section 6.1.6.4). Additionally, the sponsor should receive a sample of plasmacytoma if a 
plasmacytoma biopsy is performed for any reason, including during screening. Subjects who have 
a lumbar puncture as part of their neurologic work up should have cerebral spinal fluid for 
additional test by the sponsor. In all cases, such analyses would be specific to research related to
the study treatment(s) or diseases being investigated. If a subject dies and an autopsy is performed, 
specimens may be requested by the sponsor for analysis.
8.9.1.
Pharmacodynamic/Predictive Markers
The baseline of the JNJ-68284528 subsets and dynamic changes/persistence and activation of the 
CAR-positive viable T cells may be associated with the depth and durability of response. An 
evaluation of these cell populations may be performed by flow cytometry or cytometry by time of 
flight (CyTOF) or both and correlated with response. Additional immunophenotyping may be 
performed on bone marrow aspirate and whole blood samples to evaluate expression of biomarkers 
on myeloma cells (such as BCMA and PD-L1) and immune cell populations (such as CD4+ and 
CD8+ T cells) by flow cytometry, CyTOF or NGS (whole exome and RNA sequencing or both). 
T-cell receptor sequencing may be performed to study T-cell clonality that may affect treatment
response. Samples may be characterized by gene expression profiling and somatic mutation 
analysis by next generation sequencing (whole exome and RNA sequencing) to evaluate potential 
biomarkers that may correlate with response. Samples may be evaluated by other similar 
technologies to evaluate protein or RNA expression or for somatic DNA analysis.

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Circulating serum biomarkers present following chemotherapy conditioning and following 
infusion of CAR-T cells have been associated with response to some CAR-T cell-based therapies. 
Evaluation of cytokines (such as IL-6 and IFN-γ) and other circulating proteins (such as granzymes 
or perforin) will be analyzed to identify potential pharmacodynamic and predictive biomarkers of 
response or resistance.
8.9.2.
High-risk Classification by Cytogenetics
Bone marrow aspirate samples will be collected as specified in Schedule of Activities (Table 4 and
Table 5) and will be utilized for translocation/mutation/genomic analysis (DNA/RNA) to assess 
whether specific molecular subgroups such as del17p, t(4;14), t(14;16); Gain/Amp 1q are 
responsive to JNJ-68284528 treatment. The clinical benefit (ORR, PFS, and OS) of JNJ-68284528 
in subjects with these cytogenetic modifications or other high-risk molecular subtypes may be 
determined.
8.10.
Immunogenicity Assessments (Arm B Only)
Antibodies to JNJ-68284528 will be evaluated in serum samples collected from all subjects in the 
Arm B according to the Schedule of Activities (Table 5). Samples will also be collected at the time 
onset of suspected CRS or CAR-T cell-related neurotoxicity (ie, ICANS) regardless of causality 
(as specified in Table 5). 
Additionally, serum samples should also be collected at the final visit from subjects who 
discontinued due to PD or were withdrawn from the study. These samples will be tested by the
sponsor or sponsor’s designee. The exact dates and times of blood sampling must be recorded on 
the laboratory requisition form. Refer to the Laboratory Manual for sample collection 
requirements. Collected samples must be stored under specified controlled conditions for the 
temperatures indicated in the Laboratory Manual.
JNJ-68284528 transgene concentration will also be determined to aide in the interpretation of 
immunogenicity data. These samples will be stored and evaluated if deemed necessary.
Serum samples will be screened for antibodies binding to JNJ-68284528 and the titer of confirmed 
positive samples will be reported. Other analyses may be performed to verify the stability of 
antibodies to JNJ-68284528 and/or further characterize the immunogenicity of JNJ-68284528.
Genetic analyses will not be performed on these serum samples. Subject confidentiality will be 
maintained.
Analytical Procedures
The detection and characterization of antibodies to JNJ-68284528 will be performed using a 
validated assay method by or under the supervision of the sponsor. Other analyses may be 
performed to characterize immunogenicity.
8.11.
Patient-Reported Outcome Assessments
The subjects’ HRQoL (disease-related symptoms, functioning, and general well-being) will be 
captured using PRO measures that will be administered using an electronic tablet (ePRO) device

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at the site. These measures will be administered according to the Schedule of Activities (Table 2
to Table 5) to be completed by the subjects before any clinical tests, procedures, or other 
consultations that would influence subject’s perceptions of their current health state. The PRO 
measures will be provided in the local language. If a subject requires assistance completing the 
PRO assessment, a study coordinator may assist but should not prompt the subject in selecting 
their response. Full training documentation will be provided to site coordinators before the start of 
data collection.
If the subject is not coming into the clinic for their scheduled visit and therefore unable to complete 
the PRO questionnaires in person, the PRO can be administered by interview, via the telephone.
Samples of the PRO measures are provided in Section 10.19 to Section 10.22:
!
EORTC QLQ-C30
!
MySIm-Q
!
EQ-5D-5L
!
PGIS
!
PRO-CTCAE items
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 
(EORTC-QLQ-C30) version 3 includes 30 items in 5 functional scales (physical, role, emotional, 
cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, 
nausea/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, 
diarrhea, and financial difficulties). The recall period is 1 week (“past week”) and responses are 
reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. 
A higher score represents greater HRQoL, better functioning, and more (worse) symptoms. The 
EORTC-QLQ-C30 has been widely used among patients with MM. Reliability, validity, and 
clinically meaningful change thresholds have been demonstrated. 
The Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) is a disease-specific PRO 
assessment complementary to the EORTC-QLQ-C30. It includes 17 items resulting in a symptom 
subscale and an impact subscale. The recall period is the “past 7 days” and responses are reported 
on a 5-point verbal rating scale.
The EQ-5D-5L is a generic measure of health status. For purposes of this study, the EQ-5D-5L 
will be used to generate utility scores for use in cost-effectiveness analyses. The EQ-5D-5L is a 
5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, 
pain/discomfort and anxiety/depression plus a visual analog scale rating “health today” with 
anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The 
scores for the 5 separate questions are categorical and cannot be analyzed as cardinal numbers. 
However, the scores for the 5 dimensions are used to compute a single utility score ranging from 
zero (0.0) to 1 (1.0) representing the general health status of the individual (values less than 0 are 
possible when using the UK scoring algorithm). The EQ-5D-5L asks respondents to select their 
response based on their current health (“today”) and takes less than 5 minutes to complete. The 

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EQ-5D-5L questionnaire will continue to be completed after PD, in the post-treatment follow-up 
phase, for both Arm A and Arm B every 6 months until the end of the study. As these are not 
in-person visits, the PRO assessment will be done via telephone.
The PGIS is a single item to assess the subject’s perception in the severity of their overall health 
status using a 5-point verbal rating scale. The PGIS will be used for anchor-based meaningful 
change analyses.
The NCI’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse 
Events (PRO-CTCAE) is an item library of common adverse events experienced by people with 
cancer that are appropriate for self-reporting. Each symptom selected for inclusion can be rated by 
up to 3 attributes characterizing the presence/frequency, severity, and/or interference of the 
adverse event.34,43 For subjects with MM the following items were selected for inclusion: nausea, 
vomiting, diarrhea, shortness of breath, rash, dizziness, headache, and fatigue/tiredness/lack of 
energy. A 5-point verbal rating scale is used for subjects to select their experience based on the 
last 7 days. Responses to the PRO-CTCAE will be kept separate from CTCAE data and sites will 
not have access to the subject’s responses for real time review. Additionally, adverse event 
reporting will not be derived from the PRO data and safety analysis will not be performed using 
PRO data.
8.12.
Medical Resource Utilization and Health Economics
Health economics data such as medical resource utilization data, associated with medical 
encounters, will be collected continuously for 33 weeks, regardless of PD prior to 33 weeks, and 
reported in the eCRF by the investigator and study-site personnel. Protocol-mandated procedures, 
tests, and encounters are excluded. Health economics data such as costs associated with the 
medical encounters will be collected separately from the eCRF. All health economic data will be 
used only in a de-identified manner.
The data collected may be used to conduct exploratory economic analyses and will include:
!
Number and duration of medical care encounters, including surgeries, and other selected 
procedures (inpatient and outpatient)
!
Duration of hospitalization (total days length of stay, including duration by wards; 
eg, intensive care unit)
!
Number and character of diagnostic and therapeutic tests and procedures
!
Outpatient medical encounters and treatments (including physician or emergency room visits, 
tests and procedures, and medications)
9.
STATISTICAL CONSIDERATIONS
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general 
description of the statistical methods to be used to analyze the efficacy and safety data is outlined 
below. Specific details will be provided in the Statistical Analysis Plan.

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whichever occurs first. For subjects who have not progressed and are alive, data will be censored 
at the last disease evaluation before the start of any subsequent anti-myeloma therapy.
The primary analysis will consist of a stratified log-rank test for the comparison of the PFS 
distribution between the 2 treatment groups, stratified by the 3 factors: investigator’s choice of 
PVd vs. DPd, ISS at screening (I vs. II vs. III), and number of prior lines of therapy (1 vs. 2 or 3). 
The Kaplan-Meier method will be used to estimate the distribution of overall PFS for each 
treatment. The treatment effect (HR) and its 2-sided 95% CIs are to be estimated using a stratified 
Cox regression model with treatment as the sole explanatory variable.
9.4.3.
Secondary Endpoints
Complete response (CR)/sCR is defined as the proportion of subjects who achieve a CR or sCR 
response according to the IMWG criteria.
Overall MRD negativity is defined as the proportion of subjects who achieve MRD negativity at 
any time after the date of randomization before initiation of subsequent therapy.
Rate of MRD negativity (ie, at a 10-5 level) in subjects with CR/sCR at 12 months ±3 months is 
defined as the proportion of subjects who achieve MRD-negative status and are in CR/sCR within 
time window. 
Rate of sustained MRD negativity is defined as the proportion of subjects who achieve MRD 
negativity, confirmed minimum 1 year apart and without any examination showing MRD-positive 
status in between.
Overall survival is measured from the date of randomization to the date of the subject’s death. If 
the subject is alive or the vital status is unknown, then the subject’s data will be censored at the 
date the subject was last known to be alive.
Overall response rate (ORR) is defined as the proportion of subjects who achieve a PR or better 
according to the IMWG criteria. Response to treatment will be analyzed by a validated 
computerized algorithm. 
Progression-free survival on next-line therapy (PFS2) is defined as the time interval between the 
date of randomization and date of event, which is defined as progressive disease as assessed by 
investigator that starts after the next line of subsequent therapy, or death from any cause, whichever 
occurs first. Those who are alive and for whom a second disease progression has not been observed 
are censored at the last date of follow up. 
Time to worsening of symptoms is measured as the interval from the date of randomization to the 
start date of worsening in the MySIm-Q total symptom score. The criteria for worsening will be 
derived based on anchor-based methods using the PGIS for overall health. Death due to disease 
progression will be considered as worsening. Subjects who have not met the definition of 
worsening will be censored as of the last assessment date of the MySIm-Q. 

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The analysis methods for binary endpoints (eg, CR/sCR rate, overall MRD negativity rate, rate of 
negativity in subjects with CR/sCR at 12 months ±3 months, rate of sustained MRD negativity, 
ORR) will be conducted using stratified Cochran Mantel Haenszel test. The Mantel-Haenszel odds 
ratio will be provided along with its 2-sided 95% CI and will be provided as the measure of 
treatment effect. For time-to-event endpoints (eg, OS, PFS2, time of worsening of symptoms),
similar statistical methods will be applied as for PFS described in Section 9.4.2. 
9.4.4.
Safety Analyses
All safety analyses will be made on the Safety Population.
Adverse Events
The verbatim terms used in the eCRF by investigators to identify adverse events will be coded 
using the Medical Dictionary for Regulatory Activities. All reported TEAEs will be included in 
the analysis. For each adverse event, the percentage of subjects who experience at least 
1 occurrence of the given event will be summarized by intervention group. In addition, 
comparisons between intervention groups will be provided if appropriate.
Summaries, listings, datasets, or subject narratives may be provided, as appropriate, for those 
subjects who die, who discontinue intervention due to an adverse event, or who experience a severe 
or a serious adverse event.
Parameters with predefined NCI-CTCAE toxicity grades will be summarized except for CRS and 
CAR-T cell-related neurotoxicity (eg, ICANS). Cytokine release syndrome grading will be 
evaluated and summarized according to the ASTCT consensus grading (Section 10.25).24 CAR-T 
cell related neurotoxicity (eg, ICANS) will be graded and summarized using the ASTCT consensus 
grading (Section 10.24). In addition, all individual symptoms of CRS (eg, fever, hypotension) and 
CAR-T cell-related neurotoxicity (eg, depressed level of consciousness, seizures) captured as 
individual AEs and graded by CTCAE criteria will be also summarized. Neurotoxicity that is not 
temporally associated with CRS, or any other neurologic AEs that do not qualify as ICANS, will 
be graded and summarized by CTCAE criteria. Change from baseline to the worst AE grade 
experienced by the participant during the study will be provided as shift tables.
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. Descriptive statistics will be 
calculated for each laboratory analyte at baseline and for observed values and changes from 
baseline at each scheduled time point. Worst toxicity grade during treatment will be presented 
according to NCI-CTCAE Version 5.0. Change from baseline to the worst toxicity grade 
experienced by the subject during the study will be provided as cross-tabulations.
Electrocardiogram
The interpretation of the ECGs as determined by a qualified physician (investigator or qualified 
designee) will be summarized at scheduled time points.

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Vital Signs
Vital signs including temperature, pulse/heart rate, respiratory rate, and blood pressure (systolic 
and diastolic) will be monitored and clinically relevant changes occurring during the study will be 
recorded on the adverse event section of the eCRF. The percentage of subjects with values beyond 
clinically important limits will be summarized.
9.4.5.
Pharmacokinetic Analyses
All concentrations below the lowest quantifiable concentration or missing data will be labeled as 
such in the concentration database. Concentrations below the lowest quantifiable concentration 
will be treated as zero in the summary statistics. Descriptive statistics will be used to summarize 
CAR-T positive cell count and transgene level at each sampling timepoint. Pharmacokinetic 
parameters, including, but not limited to Cmax, AUC, and Tmax will be summarized descriptively at 
each sampling timepoint.
If sufficient data are available, population-PK analysis of peripheral JNJ-68284528 cellular 
concentration and transgene level-time data of JNJ-68284528 may be performed. If the 
population-PK analysis is conducted, details will be given in a population-PK analysis plan and 
the results of the analysis will be presented in a separate report. Exposure-response analyses may 
also be performed; if performed, details will be provided in a separate analysis plan and report.
9.4.6.
Biomarkers Analyses
Baseline bone marrow aspirate samples will be evaluated by an NGS assay to establish the 
myeloma clone (calibration), which will be used for MRD monitoring. In this study, bone marrow 
samples will be collected when a bone marrow aspirate is performed at Screening and at the 
subsequent timepoints outlined in the Schedule of Activities. Peripheral blood sample will be
collected from subjects as outlined in the Schedule of Activities and processed to plasma and 
PBMCs. If possible, bone marrow core biopsy sample (slides or block) from bone marrow biopsy 
performed at disease progression in subjects on Arm B should be sent to the central laboratory.
9.4.7.
Immunogenicity Analyses 
The incidence of anti-JNJ-68284528 antibodies will be summarized for all subjects who receive 
JNJ-68284528 and have appropriate samples for detection of antibodies to JNJ-68284528
(ie, subjects with at least 1 sample obtained after the infusion of JNJ-68284528). 
Immunogenicity analyses will be descriptive in nature and will include the number and percentage 
of subjects who developed anti-JNJ-68284528 antibodies. The effect of anti-JNJ-68284528 
antibodies on pharmacokinetics, safety, and efficacy may also be evaluated.
9.4.8.
Pharmacokinetic/Pharmacodynamic Analyses 
Pharmacokinetic/pharmacodynamic modeling may be performed, including exploring the 
relationship between serum concentrations of JNJ-68284528 and endpoints of clinical efficacy or 
safety. Details and results of any analysis performed will be presented in a separate report.

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9.4.9.
Patient-Reported Outcome Analyses 
The EORTC QLQ-C30, MySIm-Q, EQ-5D-5L utility and visual analog scores, and PGIS, will be 
descriptively summarized at each time point. Meaningful and sustained improvement in subject’s 
HRQoL comparative to their baseline health status will be evaluated using established meaningful 
change thresholds as well as anchor-based methods using the PGIS.21 Differences between 
treatment groups will be assessed by change from baseline (screening phase) using mixed models 
for repeated measures. Frequency distributions of the PRO-CTCAE items by visit will be reported.
9.4.10.
Medical Resource Utilization 
Medical resource utilization will be descriptively summarized by intervention group.
9.5.
Interim Analysis
One interim analysis for efficacy is planned for PFS. The interim analysis will be performed after 
all subjects enrolled and when approximately 188 PFS events, which is approximately 75% of the 
total planned PFS events, have been accumulated. The significance level for PFS at this interim 
analysis to establish the superiority of JNJ-68284528 over standard therapy will be determined 
based on the observed number of PFS events at the interim analysis, using the O’Brien-Fleming 
boundaries as implemented by the Lan-DeMets alpha spending method. Assuming 188 PFS events 
are observed, the alpha to be spent in this interim analysis will be 0.0193 (2-sided). If the observed 
2-sided p-value is smaller than this significance level, the superiority of JNJ-68284528 versus 
standard therapy with respect to PFS will be established. If the JNJ-68284528 Arm is numerically 
worse than that of the standard therapy arm in terms of PFS (observed hazard ratio >1, favoring 
the standard therapy arm, then the study may be terminated for futility. The final analysis of PFS 
will be performed after approximately 250 PFS events have been accumulated. The first and 
second interim analyses for OS will be performed at the same time as the interim and final analysis 
for PFS, respectively. In addition, the third interim analysis for OS will be performed when 
approximately 200 OS events have occurred. The final OS analysis will be performed at the time 
of approximately 250 OS events, which also defines the end of study. The alpha spending function 
for OS will be power spending function with parameter=2. For example, if the observed number 
of OS events is 114 at the time of the first interim analysis for PFS (ie, approximately 188 PFS 
events), the alpha to be spent for OS is 0.0104 (2-sided).
9.6.
Data Monitoring Committee or Other Review Board
An Independent Data Monitoring Committee (IDMC), will be established as noted in Committees 
Structure in Section 10.3, Regulatory, Ethical, and Study Oversight Considerations.
10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS

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10.1.
Appendix 1: Abbreviations 
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
ASTCT
aspartate aminotransferase
American Society for Transplantation and Cellular Therapy
BCMA
B-cell maturation antigen, CD269, TNFRSF17
CAR-T
chimeric antigen receptor T-cell
CI
confidence interval
COPD
chronic obstructive pulmonary disease
COVID-19
Coronavirus Disease-2019
CR
complete response
CRES
cell-related encephalopathy syndrome
CRS
cytokine release syndrome
CTCAE
Common Terminology Criteria for Adverse Events
CTPPM
Cell Therapy Product Procedures Manual
CyTOF
cytometry by time of flight
DIC
disseminated intravascular coagulation
DPd
daratumumab, pomalidomide, and dexamethasone
DSIFE
daratumumab-specific immunofixation electrophoresis
eCRF
electronic case report form
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eDC
electronic data capture
eGRF
estimated glomerular filtration rate
EORTC-QLQ-C30
European Organization for Research and Treatment of Cancer Quality of Life 
Questionnaire
EQ-5D-5L
EuroQol Five Dimension Questionnaire
EU
European Union
FEV1
forced expiratory volume in 1 second
FLC
free light chain
GCP
Good Clinical Practice
G-CSF
granulocyte colony-stimulating factor
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HLH
hemophagocytic lymphohistiocytosis
HRQoL
health-related quality of life
HTLV
human T-lymphotropic virus
IAT
Indirect Antiglobulin Test 
ICANS
Immune Effector Cell-associated Neurotoxicity Syndrome
ICE
Immune-effector Cell-associated Encephalopathy
ICF
informed consent form
ICH
International Council on Harmonisation
IDMC
Independent Data Monitoring Committee
IEC
Independent Ethics Committee
IMiDs
Immunomodulatory drugs
IMWG
International Myeloma Working Group
IPPI
investigational product preparation instructions
IRB
Institutional Review Board
IRR
infusion-related reaction
ISS
international staging system
IV
intravenous(ly)
MDRD
Modification of Diet in Renal Disease
MRD
minimal residual disease
MRI
magnetic resonance imaging
MUGA
multiple-gated acquisition
MTD
maximum tolerated dose

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NCI
National Cancer Institute
NGS
next generation sequencing
ORR
overall response rate
OS
overall survival
PBMC
peripheral blood mononuclear cells
PD
progressive disease/progression of disease
PET
positron emission tomography
PFS
progression-free survival
PFS2
PFS on next-line therapy
PGIS
Patient Global Impression of Severity
PIs
proteasome inhibitors
PK
pharmacokinetic(s)
PO
oral(ly)
PPI
proton pump inhibitor
PQC
Product Quality Complaint
PR
partial response
PRO
patient-reported outcome(s)
PRO-CTCAE
Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse 
Events
PVd
pomalidomide, bortezomib, and dexamethasone
RCL
replication competent lentivirus
rHuPH20
recombinant human hyaluronidase PH20
SC
subcutaneous
sCR
stringent complete response
SIPPM
site investigational product procedures manual
SmPC
Summary of Product Characteristics
SPEP
serum protein electrophoresis
SPM
second primary malignancy
SUSAR
suspected unexpected serious adverse reaction
TEAE
treatment-emergent adverse event
UPEP
urine protein electrophoresis
WOPBP
women of child bearing potential
Definitions of Terms 
AUC
area under the peripheral blood concentration-time curve
AUCinf
AUC from time 0 to infinity
AUC(0-t) 
AUC from time 0 to t
Cmax
maximum peripheral blood concentration
Tmax
time to reach maximum peripheral blood concentration

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Tests within 60 days prior to 
randomization
HIV, Hepatitis B, Hepatitis C, HCV RNA, HTLV, and other infectious disease 
as applicable per local regulations
Test prior to daratumumab 
administration 
Indirect Antiglobulin Test (IAT) (see further description below)
COVID-19 antibody titer 
(optional)
As applicable per institutional standards, up to 1 year post cilta-cel infusion.
Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; +-hCG=+-human chorionic 
gonadotropin; CBC=complete blood count; eGFR=estimated glomerular filtration rate; HBsAg=hepatitis B surface 
antigen; anti-HBc=anti-hepatitis B core antibody, anti-HBs=anti-hepatitis B surface antibody; HCV=hepatitis C virus; 
HTLV= human T-lymphotropic virus; MDRD=Modification of Diet in Renal Disease.
a
CD4/CD8 panel should be done for newly enrolled subjects. Subjects enrolled under amendment #1 that have re-
consented to amendment #2 and have received cilta-cel are not required to do the CD4/CD8 lymphocyte panel.
b.
Direct bilirubin if Gilbert’s disease. 
c.
Calculated using MDRD formula (see Section 10.11) only to be included at screening.
d.
Calculated using MDRD formula (see Section 10.11) only to be included prior to conditioning regimen
Indirect Antiglobulin Test (IAT) 
Blood Type, Rh, and Indirect Antiglobulin Test (IAT) should be done before the first dose of 
daratumumab. Subject RBC phenotyping (standard or extended) is an alternative option to the IAT 
test, if locally required. Either method must be completed prior to first study drug administration.
Daratumumab interferes with the IAT, which is a routine pre-transfusion test performed to identify 
a subject's antibodies to minor antigens so that suitable donor blood can be given for transfusion. 
Daratumumab does not interfere with ABO/RhD typing. CD38 is expressed at very low levels on 
erythrocytes. Daratumumab binds to the CD38 on erythrocytes, which results in a positive IAT 
(Indirect Coombs Test). This positive result masks the detection of antibodies to minor antigens 
and may prevent or delay blood banks from issuing donor blood for transfusion. This effect occurs 
during daratumumab treatment and for up to 6 months after treatment ends. Subjects will receive 
a subject identification wallet card for the study that includes the blood profile (ABO, Rh, and IAT 
or phenotyping) determined before the first study drug administration, along with information on 
the IAT interference for healthcare providers/blood banks. Subjects are to carry this card 
throughout the treatment period and for at least 6 months after treatment ends. Blood banks can 
eliminate the daratumumab interference with IAT by treating reagent RBCs with dithiothreitol 
(DTT).7,8
Possible methods for blood banks to provide safe RBCs for transfusion to subjects receiving 
daratumumab include:
a.
Providing ABO/RhD compatible, phenotypically (standard or extended phenotyping) or 
genotypically matched units
b. Providing ABO/RhD compatible, K-negative units after ruling out or identifying 
alloantibodies using DTT-treated reagent RBCs
Uncrossmatched, ABO/RhD compatible RBC units should be administered if transfusion is needed 
emergently as per local blood bank practice.
Despite daratumumab binding to CD38 on erythrocytes, no indication of clinically significant 
hemolysis has been observed in daratumumab studies. For additional details, refer to the 
daratumumab Investigator's Brochure (IB daratumumab).

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10.3.
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations
REGULATORY AND ETHICAL CONSIDERATIONS
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and 
country-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting studies that involve the participation of human subjects. 
Compliance with this standard provides public assurance that the rights, safety, and well-being of 
study subjects are protected, consistent with the principles that originated in the Declaration of 
Helsinki, and that the study data are credible.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment by 
the sponsor. All protocol amendments must be issued by the sponsor, and signed and dated by the 
investigator. Protocol amendments must not be implemented without prior IEC/IRB approval, or 
when the relevant competent authority has raised any grounds for non-acceptance, except when 
necessary to eliminate immediate hazards to the subjects, in which case the amendment must be 
promptly submitted to the IEC/IRB and relevant competent authority. Documentation of 
amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When the 
change(s) involve only logistic or administrative aspects of the study, the IEC/IRB (where 
required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the appropriate sponsor representative 
listed in the Contact Information page(s), which will be provided as a separate document. Except 
in emergency situations, this contact should be made before implementing any departure from the 
protocol. In all cases, contact with the sponsor must be made as soon as possible to discuss the 
situation and agree on an appropriate course of action. The data recorded in the electronic Case 
Report Form (eCRF) and source documents will reflect any departure from the protocol, and the 
source documents will describe this departure and the circumstances requiring it.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities 
in each respective country, if applicable. A study may not be initiated until all local regulatory 
requirements are met.

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Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study intervention 
to the study site:
!
Protocol and amendment(s), if any, signed and dated by the principal investigator
!
A copy of the dated and signed (or sealed, where appropriate per local regulations), written 
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if 
applicable, subject compensation programs. This approval must clearly identify the specific 
protocol by title and number and must be signed (or sealed, where appropriate per local 
regulations) by the chairman or authorized designee.
!
Name and address of the IEC/IRB, including a current list of the IEC/IRB members and their 
function, with a statement that it is organized and operates according to GCP and the 
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, from 
the IEC/IRB, a general statement may be substituted for this list. If an investigator or a 
member of the study-site personnel is a member of the IEC/IRB, documentation must be 
obtained to state that this person did not participate in the deliberations or in the vote/opinion 
of the study.
!
Regulatory authority approval or notification, if applicable
!
Signed and dated statement of investigator (eg, Form FDA 1572), if applicable
!
Documentation of investigator qualifications (eg, curriculum vitae)
!
Completed investigator financial disclosure form from the principal investigator, where 
required
!
Signed and dated clinical trial agreement, which includes the financial agreement
!
Any other documentation required by local regulations
The following documents must be provided to the sponsor before enrollment of the first subject:
!
Completed investigator financial disclosure forms from all subinvestigators
!
Documentation of subinvestigator qualifications (eg, curriculum vitae)
!
Name and address of any local laboratory conducting tests for the study, and a dated copy of 
current laboratory normal ranges for these tests, if applicable
!
Local 
laboratory 
documentation 
demonstrating 
competence 
and 
test 
reliability
(eg, accreditation/license), if applicable
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the IEC/IRB 
with current and complete copies of the following documents (as required by local regulations):
!
Final protocol and, if applicable, amendments
!
Sponsor-approved ICF (and any other written materials to be provided to the subjects)
!
IB (or equivalent information) and amendments/addenda

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!
Sponsor-approved subject recruiting materials
!
Information on compensation for study-related injuries or payment to subjects for 
participation in the study, if applicable
!
Investigator's curriculum vitae or equivalent information (unless not required, as documented 
by the IEC/IRB)
!
Information regarding funding, name of the sponsor, institutional affiliations, other potential 
conflicts of interest, and incentives for subjects
!
Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final protocol, 
amendments (if any, excluding the ones that are purely administrative, with no consequences for 
subjects, data or study conduct, unless required locally), the ICF, applicable recruiting materials, 
and subject compensation programs, and the sponsor has received a copy of this approval. This 
approval letter must be dated and must clearly identify the IEC/IRB and the documents being 
approved.
During the study the investigator (or sponsor where required) will send the following documents 
and updates to the IEC/IRB for their review and approval, where appropriate:
!
Protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct)
!
Revision(s) to ICF and any other written materials to be provided to subjects
!
If applicable, new or revised subject recruiting materials approved by the sponsor
!
Revisions to compensation for study-related injuries or payment to subjects for participation 
in the study, if applicable
!
New edition(s) of the IB and amendments/addenda
!
Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually)
!
Reports of adverse events that are serious, unlisted/unexpected, and associated with the study 
intervention
!
New information that may adversely affect the safety of the subjects or the conduct of the 
study
!
Deviations from or changes to the protocol to eliminate immediate hazards to the subjects
!
Report of deaths of subjects under the investigator's care
!
Notification if a new investigator is responsible for the study at the site
!
Development Safety Update Report and Line Listings, where applicable
!
Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct), the amendment and applicable ICF revisions 

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must be submitted promptly to the IEC/IRB for review and approval before implementation of the 
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about 
the study completion (if applicable, the notification will be submitted through the head of 
investigational institution).
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.1.
FINANCIAL DISCLOSURE
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information in accordance with local regulations to allow the sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) for details on financial disclosure.
INFORMED CONSENT PROCESS 
Each subject (or a legally acceptable representative) must give written consent according to local 
requirements after the nature of the study has been fully explained. The ICF(s) must be signed
before performance of any study-related activity. The ICF(s) that is/are used must be approved by 
both the sponsor and by the reviewing IEC/IRB and be in a language that the subject can read and 
understand. The informed consent should be in accordance with principles that originated in the 
Declaration of Helsinki, current ICH and GCP guidelines, applicable regulatory requirements, and 
sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study-site 
personnel must explain to potential subjects or their legally acceptable representatives the aims, 
methods, reasonably anticipated benefits, and potential hazards of the study, and any discomfort 
participation in the study may entail. Subjects will be informed that their participation is voluntary 
and that they may withdraw consent to participate at any time. They will be informed that choosing 
not to participate will not affect the care the subject will receive for the treatment of his or her 
disease. Subjects will be told that alternative treatments are available if they refuse to take part and 
that such refusal will not prejudice future treatment. Finally, they will be told that the investigator 
will maintain a subject identification register for the purposes of long-term follow up if needed 
and that their records may be accessed by health authorities and authorized sponsor personnel 
without violating the confidentiality of the subject, to the extent permitted by the applicable law(s) 
or regulations. By signing the ICF the subject or legally acceptable representative is authorizing 
such access, which includes permission to obtain information about his or her survival status]. It 
also denotes that the subject agrees to allow his or her study physician to recontact the subject for 

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the purpose of obtaining consent for additional safety evaluations, and subsequent disease-related 
treatments, if needed.
The subject or legally acceptable representative will be given sufficient time to read the ICF and 
the opportunity to ask questions. After this explanation and before entry into the study, consent 
should be appropriately recorded by means of either the subject's or his or her legally acceptable 
representative's personally dated signature. After having obtained the consent, a copy of the ICF 
must be given to the subject.
Subjects who are rescreened are required to sign a new ICF.
If the subject or legally acceptable representative is unable to read or write, an impartial witness 
should be present for the entire informed consent process (which includes reading and explaining 
all written information) and should personally date and sign the ICF after the oral consent of the 
subject or legally acceptable representative is obtained.
DATA PROTECTION
Privacy of Personal Data
The collection and processing of personal data from subjects enrolled in this study will be limited 
to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality 
and compliance with applicable data privacy protection laws and regulations. Appropriate 
technical and organizational measures to protect the personal data against unauthorized disclosures 
or access, accidental or unlawful destruction, or accidental loss or alteration must be put in place. 
Sponsor personnel whose responsibilities require access to personal data agree to keep the identity 
of subjects confidential.
The informed consent obtained from the subject (or his or her legally acceptable representative) 
includes explicit consent for the processing of personal data and for the investigator/institution to 
allow direct access to his or her original medical records (source data/documents) for study-related 
monitoring, audit, IEC/IRB review, and regulatory inspection. This consent also addresses the 
transfer of the data to other entities and to other countries.
The subject has the right to request through the investigator access to his or her personal data and 
the right to request rectification of any data that are not correct or complete. Reasonable steps will 
be taken to respond to such a request, taking into consideration the nature of the request, the 
conditions of the study, and the applicable laws and regulations.
Exploratory DNA, pharmacodynamics, biomarker, PK, and immunogenicity research is not 
conducted under standards appropriate for the return of data to subjects. In addition, the sponsor 
cannot make decisions as to the significance of any findings resulting from exploratory research. 
Therefore, exploratory research data will not be returned to subjects or investigators, unless 

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required by law or local regulations. Privacy and confidentiality of data generated in the future on 
stored samples will be protected by the same standards applicable to all other clinical data.
LONG-TERM RETENTION OF SAMPLES FOR ADDITIONAL FUTURE RESEARCH
Samples, including apheresis product, collected in this study and JNJ-68284528 that was 
manufactured but not administered to a subject may be stored for up to 15 years (or according to 
local regulations) for additional research. Samples will only be used to understand JNJ-68284528, 
to understand MM, to understand differential treatment responders, and to develop tests/assays 
related to JNJ-68284528. The research may begin at any time during the study or the post-study 
storage period. 
Stored samples will be coded throughout the sample storage and analysis process and will not be 
labeled with personal identifiers. Subjects may withdraw their consent for their samples to be
stored for research (refer to Section 7.2, Withdrawal From the Use of Research Samples).
COMMITTEES STRUCTURE
Data Monitoring Committee
An IDMC, consisting of 2 clinicians and 1 statistician, will be established to review efficacy and 
safety results at the planned interim analysis for the primary efficacy endpoint. After each interim 
review, the IDMC will make recommendations regarding any required modifications for the study. 
In addition, the IDMC will review cumulative safety data (ie, serious adverse events) after the first 
20 subjects with at least 3 months follow up after randomization. Thereafter, the IDMC will review 
the cumulative safety data every 6 months. The details will be provided in a separate IDMC charter.
PUBLICATION POLICY/DISSEMINATION OF CLINICAL STUDY DATA
All information, including but not limited to information regarding JNJ-68284528 or the sponsor's 
operations (eg, patent application, formulas, manufacturing processes, basic scientific data, prior 
clinical data, formulation information) supplied by the sponsor to the investigator and not 
previously published, and any data, including exploratory biomarker research data, generated as a 
result of this study, are considered confidential and remain the sole property of the sponsor. The 
investigator agrees to maintain this information in confidence and use this information only to 
accomplish this study and will not use it for other purposes without the sponsor's prior written 
consent.
The investigator understands that the information developed in the study will be used by the 
sponsor in connection with the continued development of JNJ-68284528, and thus may be 
disclosed as required to other clinical investigators or regulatory agencies. To permit the 
information derived from the clinical studies to be used, the investigator is obligated to provide 
the sponsor with all data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the sponsor and 
will contain data from all study sites that participated in the study as per protocol. Recruitment 
performance or specific expertise related to the nature and the key assessment parameters of the 

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study will be used to determine a coordinating investigator for the study. Results of exploratory 
biomarker analyses performed after the Clinical Study Report has been issued will be reported in 
a separate report and will not require a revision of the Clinical Study Report. 
Study subject identifiers will not be used in publication of results. Any work created in connection 
with performance of the study and contained in the data that can benefit from copyright protection 
(except any publication by the investigator as provided for below) shall be the property of the 
sponsor as author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal 
Editors (ICMJE) guidelines, the sponsor shall have the right to publish such primary (multicenter) 
data and information without approval from the investigator. The investigator has the right to 
publish study site-specific data after the primary data are published. If an investigator wishes to 
publish information from the study, a copy of the manuscript must be provided to the sponsor for 
review at least 60 days before submission for publication or presentation. Expedited reviews will 
be arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in 
writing, the investigator will withhold such publication for up to an additional 60 days to allow for 
filing of a patent application. In the event that issues arise regarding scientific integrity or 
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor will 
not mandate modifications to scientific content and does not have the right to suppress information. 
For multicenter study designs and sub-study approaches, secondary results generally should not 
be published before the primary endpoints of a study have been published. Similarly, investigators 
will recognize the integrity of a multicenter study by not submitting for publication data derived 
from the individual study site until the combined results from the completed study have been 
submitted for publication, within 18 months after the study end date, or the sponsor confirms there 
will be no multicenter study publication. Authorship of publications resulting from this study will 
be based on the guidelines on authorship, such as those described in the ICMJE Recommendations 
for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals, which 
state that the named authors must have made a significant contribution to the conception or design 
of the work; or the acquisition, analysis, or interpretation of the data for the work; and drafted the 
work or revised it critically for important intellectual content; and given final approval of the 
version to be published; and agreed to be accountable for all aspects of the work in ensuring that 
questions related to the accuracy or integrity of any part of the work are appropriately investigated 
and resolved.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required 
by law. The disclosure of the final study results will be performed after the end of study in order 
to ensure the statistical analyses are relevant.

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DATA QUALITY ASSURANCE
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified 
investigators and appropriate study sites, review of protocol procedures with the investigator and 
study-site personnel before the study, and periodic monitoring visits by the sponsor, and direct 
transmission of clinical laboratory data from a central laboratory into the sponsor's data base. 
Written instructions will be provided for collection, handling, storage, and shipment of samples. 
Guidelines for eCRF completion will be provided and reviewed with study-site personnel before 
the start of the study. The sponsor will review eCRF for accuracy and completeness during on-site 
monitoring visits and after transmission to the sponsor; any discrepancies will be resolved with the 
investigator or designee, as appropriate. After upload of the data into the study database they will 
be verified for accuracy and consistency with the data sources.
CASE REPORT FORM COMPLETION
Case report forms are prepared and provided by the sponsor for each subject in electronic format. 
All data relating to the study must be recorded in the eCRF. All eCRF entries, corrections, and 
alterations must be made by the investigator or authorized study-site personnel. The investigator 
must verify that all data entries in the eCRF are accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an 
eCRF. Study-specific data will be transmitted in a secure manner to the sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any 
such worksheets will become part of the subject's source documents. Data must be entered into 
eCRF in English. The eCRF must be completed as soon as possible after a subject visit and the 
forms should be available for review at the next scheduled monitoring visit.
All participative measurements (eg, pain scale information or other questionnaires) will be 
completed by the same individual who made the initial baseline determinations whenever possible.
If necessary, queries will be generated in the eDC tool. If corrections to an eCRF are needed after 
the initial entry into the eCRF, this can be done in either of the following ways:
!
Investigator and study-site personnel can make corrections in the eDC tool at their own 
initiative or as a response to an auto query (generated by the eDC tool).
!
Sponsor or sponsor delegate can generate a query for resolution by the investigator and study-
site personnel.
SOURCE DOCUMENTS
At a minimum, source documents consistent in the type and level of detail with that commonly 
recorded at the study site as a basis for standard medical care must be available for the following: 
subject identification, eligibility, and study identification; study discussion and date of signed 
informed consent; dates of visits; results of safety and efficacy parameters as required by the 

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protocol; record of all adverse events and follow-up of adverse events; concomitant medication; 
intervention receipt/dispensing/return records; study intervention administration information; and 
date of study completion and reason for early discontinuation of study intervention or withdrawal 
from the study, if applicable. 
The author of an entry in the source documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be 
reviewed with the investigator before the study and will be described in the monitoring guidelines 
(or other equivalent document).
The minimum source documentation requirements for Section 5.1, Inclusion Criteria and 
Section 5.2, Exclusion Criteria that specify a need for documented medical history are as follows:
!
Referral letter from treating physician or
!
Complete history of medical notes at the site
!
Discharge summaries
Inclusion and exclusion criteria not requiring documented medical history must be verified at a 
minimum by subject interview or other protocol required assessment (eg, physical examination, 
laboratory assessment) and documented in the source documents.
An eSource system may be utilized, which contains data traditionally maintained in a hospital or 
clinic record to document medical care (eg, electronic source documents) as well as the clinical 
study-specific data fields as determined by the protocol. This data is electronically extracted for 
use by the sponsor. If eSource is utilized, references made to the eCRF in the protocol include the 
eSource system but information collected through eSource may not be limited to that found in the 
eCRF.
MONITORING
The sponsor will use a combination of monitoring techniques central, remote, or on-site monitoring 
to monitor this study.
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will 
record dates of the visits in a study site visit log that will be kept at the study site. The first 
post-initiation visit will be made as soon as possible after enrollment has begun. At these visits, 
the monitor will compare the data entered into the eCRF with the source documents 
(eg, hospital/clinic/physician’s office medical records). The nature and location of all source 
documents will be identified to ensure that all sources of original data required to complete the 
eCRF are known to the sponsor and study-site personnel and are accessible for verification by the 
sponsor study-site contact. If electronic records are maintained at the study site, the method of 
verification must be discussed with the study-site personnel. 
Direct access to source documents (medical records) must be allowed for the purpose of verifying 
that the recorded data are consistent with the original source data. Findings from this review will 

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be discussed with the study-site personnel. The sponsor expects that, during monitoring visits, the 
relevant study-site personnel will be available, the source documents will be accessible, and a 
suitable environment will be provided for review of study-related documents. The monitor will 
meet with the investigator on a regular basis during the study to provide feedback on the study 
conduct.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during these 
remote contacts, study-site personnel will be available to provide an update on the progress of the 
study at the site. 
Central monitoring will take place for data identified by the sponsor as requiring central review.
ON-SITE AUDITS
Representatives of the sponsor's clinical quality assurance department may visit the study site at 
any time during or after completion of the study to conduct an audit of the study in compliance 
with regulatory guidelines and company policy. These audits will require access to all study 
records, including source documents, for inspection. Subject privacy must, however, be respected. 
The investigator and study-site personnel are responsible for being present and available for 
consultation during routinely scheduled study-site audit visits conducted by the sponsor or its 
designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part 
of a national GCP compliance program or to review the results of this study in support of a 
regulatory submission. The investigator should immediately notify the sponsor if he or she has 
been contacted by a regulatory agency concerning an upcoming inspection.
RECORD RETENTION
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF
and all source documents that support the data collected from each subject, as well as all study 
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical 
Trial, and all study documents as specified by the applicable regulatory requirement(s). The 
investigator/institution will take measures to prevent accidental or premature destruction of these 
documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing applications 
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical 
development of the investigational product. These documents will be retained for a longer period 
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the 
responsibility of the sponsor to inform the investigator/institution as to when these documents no 
longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will accept 
the responsibility. The sponsor must be notified in writing of the name and address of the new 

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custodian. Under no circumstance shall the investigator relocate or dispose of any study documents 
before having obtained written approval from the sponsor.
STUDY AND SITE START AND CLOSURE
First Act of Recruitment
The first site open is considered the first act of recruitment and it becomes the study start date.
Study Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A 
study site is considered closed when all required documents and study supplies have been collected 
and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are not 
limited to:
!
Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or 
local health authorities, the sponsor's procedures, or GCP guidelines
!
Inadequate recruitment of subjects by the investigator
!
Discontinuation of further study intervention development

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10.4.
Appendix 4: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
ADVERSE EVENT DEFINITIONS AND CLASSIFICATIONS
Adverse Event
An adverse event is any untoward medical occurrence in a clinical study subject administered a 
medicinal (investigational or non-investigational) product. An adverse event does not necessarily 
have a causal relationship with the intervention. An adverse event can therefore be any unfavorable 
and unintended sign (including an abnormal finding), symptom, or disease temporally associated 
with the use of a medicinal (investigational or non-investigational) product, whether or not related 
to that medicinal (investigational or non-investigational) product. (Definition per International 
Council on Harmonisation [ICH])
This includes any occurrence that is new in onset or aggravated in severity or frequency from the 
baseline condition, or abnormal results of diagnostic procedures, including laboratory test 
abnormalities.
Note: The sponsor collects adverse events starting with the signing of the ICF (refer to All Adverse 
Events under Section 8.3, Time Period and Frequency for Collecting Adverse Events and Serious 
Adverse Events Information, for time of last adverse event recording).
Serious Adverse Event
A serious adverse event based on ICH and EU Guidelines on Pharmacovigilance for Medicinal
Products for Human Use is any untoward medical occurrence that at any dose:
!
Results in death
!
Is life-threatening
(The subject was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe.)
!
Requires inpatient hospitalization or prolongation of existing hospitalization
!
Results in persistent or significant disability/incapacity
!
Is a congenital anomaly/birth defect
!
Is a suspected transmission of any infectious agent via a medicinal product
!
Is Medically Important*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
also appropriate in other situations, such as important medical events that may not be immediately 
life threatening or result in death or hospitalization but may jeopardize the subject or may require 
intervention to prevent one of the other outcomes listed in the definition above. These should 
usually be considered serious.
If a serious and unexpected adverse event occurs for which there is evidence suggesting a causal 
relationship between the study intervention and the event (eg, death from anaphylaxis), the event 

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must be reported as a serious and unexpected suspected adverse reaction even if it is a component 
of the study endpoint (eg, all-cause mortality). 
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An adverse event is considered unlisted if the nature or severity is not consistent with the applicable 
product reference safety information. For JNJ-68284528 and daratumumab, the expectedness of 
an adverse event will be determined by whether or not it is listed in the IB. For dexamethasone, 
bortezomib, and pomalidomide, with a marketing authorization, the expectedness of an adverse 
event will be determined by whether or not it is listed in the respective PI or SmPC.
Adverse Event Associated with the Use of the Intervention
An adverse event is considered associated with the use of the study treatment if the attribution is 
related by the definitions listed below (see Attribution Definitions).
ATTRIBUTION DEFINITIONS
Assessment of Causality
The causal relationship to study treatment is determined by the Investigator. The following 
selection should be used to assess all adverse events (AE).
Related
There is a reasonable causal relationship between study treatment administration and the AE.
Not Related
There is not a reasonable causal relationship between study treatment administration and the AE.
The term "reasonable causal relationship" means there is evidence to support a causal relationship.
SEVERITY CRITERIA
An assessment of severity grade will be made by the investigator according to the NCI-CTCAE 
Version 5.0, with the exception of CRS and CAR-T cell-related neurotoxicity (eg, ICANS). 
Cytokine release syndrome should be evaluated according to the ASTCT consensus grading 
(Section 10.25). CAR-T cell-related neurotoxicity (eg, ICANS) should be graded using the 
ASTCT consensus grading (Section 10.24).24 In addition to capturing ICANS and CRS adverse 
events (graded by ASTCT consensus grading), all individual symptoms of CRS (eg, fever, 
hypotension) and CAR-T cell-related neurotoxicity (eg, depressed level of consciousness, 
seizures) must be captured as individual adverse events and graded by CTCAE criteria. Changes 
in handwriting (ie, micrographia, dysgraphia, or agraphia) should be graded using the criteria 
outlined in Section 10.27. Other neurotoxicities will be graded by CTCAE criteria. Any adverse 
events or serious adverse events not listed in the NCI-CTCAE Version 5.0 will be graded according 
to investigator clinical judgement by using the standard grades as follows:

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Grade 1
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.
Grade 2
Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living.*
Grade 3
Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily 
living.**
Grade 4
Life-threatening consequences; urgent intervention indicated.
Grade 5
Death related to adverse event.
Activities of Daily Living (ADL)
*
Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc.
**
Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, 
and not bedridden.
The investigator should use clinical judgment in assessing the severity of events not directly
experienced by the participant (eg, laboratory abnormalities).
All Grade 3 or 4 adverse events that have not resolved by the protocol-defined adverse event
collection period, or that have not resolved upon discontinuation of the subject's participation in
the study, must be followed until any of the following occurs:
!
The event resolves
!
The event stabilizes
!
The event returns to baseline, if a baseline value/status is available
!
The event can be attributed to agents other than the study intervention or to factors unrelated 
to study conduct
!
It becomes unlikely that any additional information can be obtained (subject or health care 
practitioner refusal to provide additional information, lost to follow-up after demonstration of 
due diligence with follow-up efforts)
SPECIAL REPORTING SITUATIONS
Safety events of interest on a sponsor study intervention in an interventional study that may require 
expedited reporting or safety evaluation include, but are not limited to:
!
Overdose of a sponsor study intervention
!
Suspected abuse/misuse of a sponsor study intervention
!
Accidental or occupational exposure to a sponsor study intervention
!
Medication error involving a sponsor product (with or without subject/patient exposure to the 
sponsor study intervention, eg, name confusion)
!
Exposure to a sponsor study intervention from breastfeeding

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In the event of a special reporting situation, the investigator or treating physician should contact 
the sponsor and closely monitor for AEs. Special reporting situations should be recorded in the 
eCRF. Since JNJ-68284528 will be individually manufactured and provided by the sponsor for 
complete administration in a single infusion, overdose with cilta-cel is not applicable for this study. 
Any special reporting situation that meets the criteria of an AE, including SAE, should be recorded 
on the AE/SAE page of the eCRF. Serious AEs should follow the 24-hour SAE reporting process
(Section 8.3).
PROCEDURES
All Adverse Events
All adverse events, regardless of seriousness, severity, or presumed relationship to study 
intervention, must be recorded using medical terminology in the source document and the eCRF. 
Whenever possible, diagnoses should be given when signs and symptoms are due to a common 
etiology (eg, cough, runny nose, sneezing, sore throat, and head congestion should be reported as 
"upper respiratory infection"). The exceptions are CRS and JNJ-68284528-related neurotoxicity, 
all symptoms associated with these events will be collected in the eCRF. Investigators must record 
in the eCRF their opinion concerning the relationship of the adverse event to study therapy. All 
measures required for adverse event management must be recorded in the source document and 
reported according to sponsor instructions.
For all studies with an outpatient phase, including open-label studies, the subject must be provided 
with a "wallet (study) card" and instructed to carry this card with them for the duration of the study 
indicating the following: 
!
Study number
!
Statement, in the local language(s), that the subject is participating in a clinical study
!
Investigator's name and 24-hour contact telephone number
!
Local sponsor's name and 24-hour contact telephone number (for medical personnel only)
!
Site number
!
Subject number
!
Any other information that is required to do an emergency breaking of the blind
Serious Adverse Events
All serious adverse events that have not resolved by the protocol-defined adverse event period, or
that have not resolved upon discontinuation of the subject's participation in the study, must be 
followed until any of the following occurs:
!
The event resolves
!
The event stabilizes
!
The event returns to baseline, if a baseline value/status is available

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!
The event can be attributed to agents other than the study intervention or to factors unrelated 
to study conduct
!
It becomes unlikely that any additional information can be obtained (subject or health care 
practitioner refusal to provide additional information, lost to follow-up after demonstration of 
due diligence with follow-up efforts)
Suspected transmission of an infectious agent by a medicinal product will be reported as a serious 
adverse event. Any event requiring hospitalization (or prolongation of hospitalization) that occurs 
during the course of a subject's participation in a study must be reported as a serious adverse event, 
except hospitalizations for the following:
!
Routine monitoring hospitalizations post-infusion required per protocol
!
Hospitalizations not intended to treat an acute illness or adverse event (eg, social reasons such 
as pending placement in long-term care facility)
!
Surgery or procedure planned before entry into the study (must be documented in the eCRF). 
Note: Hospitalizations that were planned before the signing of the ICF, and where the 
underlying condition for which the hospitalization was planned has not worsened, will not be 
considered serious adverse events. Any adverse event that results in a prolongation of the 
originally planned hospitalization is to be reported as a new serious adverse event.
!
The investigator may choose to hospitalize the subject per institutional standards for CAR-T 
therapy and in accordance to the criteria provided in Section 10.16.
!
The administration of blood or platelet transfusions. Hospitalization or prolonged 
hospitalization for a complication of such transfusion remains a reportable serious adverse 
event.
Expected PD should not be considered an adverse event (or serious adverse event). However, if 
determined by the investigator to be more likely related to the study treatment than the underlying 
disease, the clinical signs or symptoms of progression and the possibility that the study treatment 
is enhancing disease progression, should be reported per the usual reporting requirements.
All deaths not related to PD occurring at any time of the study after receiving JNJ-68284528, 
should be reported to the sponsor following expedited reporting procedures.
CONTACTING SPONSOR REGARDING SAFETY
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding safety issues or questions regarding the study are listed in the Contact Information 
page(s), which will be provided as a separate document.
PRODUCT QUALITY COMPLAINT HANDLING
A product quality complaint (PQC) is defined as any suspicion of a product defect related to 
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality, 
durability, or reliability of a product, including its labeling or package integrity. A PQC may have 
an impact on the safety and efficacy of the product. Timely, accurate, and complete reporting and 
analysis of PQC information from studies are crucial for the protection of subjects, investigators, 

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and the sponsor, and are mandated by regulatory agencies worldwide. The sponsor has established 
procedures in conformity with regulatory requirements worldwide to ensure appropriate reporting 
of PQC information; all studies conducted by the sponsor or its affiliates will be conducted in 
accordance with those procedures.
Procedures
All initial PQCs must be reported to the sponsor by the study-site personnel within 24 hours after 
being made aware of the event.
If the defect is combined with a serious adverse event, the study-site personnel must report the 
PQC to the sponsor according to the serious adverse event reporting timelines (refer to 
Section 8.3.1, Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information). A sample of the suspected product should be maintained for further 
investigation if requested by the sponsor.
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding product quality issues are listed in the Contact Information page(s), which will be 
provided as a separate document.

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b
In some cases it is possible that the original M protein light-chain isotype is still detected on immunofixation but the 
accompanying heavy-chain component has disappeared; this would not be considered as a CR even though the heavy-
chain component is not detectable, since it is possible that the clone evolved to one that secreted only light chains. Thus, if 
a subject has IgA lambda myeloma, then to qualify as CR there should be no IgA detectable on serum or urine 
immunofixation; if free lambda is detected without IgA, then it must be accompanied by a different heavy chain isotype 
(IgG, IgM, etc.).
c
Patients with 0.5-1.0 g/dL at baseline cannot be assessed for minimal response.
d
Clarifications to the criteria for coding progressive disease: bone marrow criteria for progressive disease are to be used 
only in subjects without measurable disease by M-protein and by FLC levels; “25% increase” refers to M-protein, and 
FLC, and does not refer to bone lesions, or soft tissue plasmacytomas and the “lowest response value” does not need to be 
a confirmed value.
Notes: All response categories (CR, sCR, VGPR, PR, MR, and progressive disease) require 2 consecutive assessments made 
at any time before the institution of any new therapy; CR, sCR, VGPR, PR, MR, and stable disease categories also require no 
known evidence of progressive or new bone lesions if radiographic studies were performed. VGPR and CR categories require 
serum and urine studies regardless of whether disease at baseline was measurable on serum, urine, both, or neither.
Radiographic studies are not required to satisfy these response requirements. Bone marrow assessments need not be 
confirmed. For progressive disease, serum M-component increases of ≥1 g/dL are sufficient to define relapse if lowest M-
component is ≥5 g/dL.
Source: Adapted from Durie (2015) Rajkumar (2011), and Kumar (2016)14,22,35

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10.8.
Appendix 8: International Myeloma Working Group Diagnostic Criteria
Diagnostic criteria for myeloma must be met when the subject was diagnosed. Multiple myeloma is defined 
as clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytomaa and 
any one or more of the following myeloma-defining events:
!
Myeloma defining events:
)
Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative 
disorder, specifically:
o
C: Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of 
normal or >2.75 mmol/L (>11 mg/dL)
o
R: Renal insufficiency: creatinine clearance <40 mL per minb or serum creatinine 
>177 μmol/L (>2 mg/dL)
o
A: Anemia: hemoglobin value of >20 g/L below the lower limit of normal, or a hemoglobin 
value <100 g/L 
o
B: Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or positron 
emission tomography-CT (PET-CT)c,d
!
Any one or more of the following biomarkers of malignancy: 
)
Clonal bone marrow plasma cell percentagea ≥60%
)
Involved:uninvolved serum free light chain ratioe ≥100
)
>1 focal lesions on MRI studiesf
a
Clonality should be established by showing κ/λ-light-chain restriction on flow cytometry, 
immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably 
be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the 
highest value should be used.
b
Measured or estimated by validated equations. 
c
If bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish 
from solitary plasmacytoma with minimal marrow involvement.
d
PET-CT=18F-fluorodeoxyglucose PET with CT.
e
These values are based on the serum Freelite assay (The Binding Site Group, Birmingham, UK). The 
involved free light chain must be ≥100 mg/L. 
f
Each focal lesion must be 5 mm or more in size.
Source: Rajkumar 201435

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10.9.
Appendix 9: Prior Multiple Myeloma Therapy Lines
A line of therapy is defined as one or more cycles of a planned treatment program. This may consist 
of one or more planned cycles of single-agent therapy or combination therapy, as well as a 
sequence of treatments administered in a planned manner. For example, a planned treatment 
approach of induction therapy followed by autologous stem cell transplantation, followed by 
maintenance is considered one line of therapy. A new line of therapy starts when a planned course 
of therapy is modified to include other treatment agents (alone or in combination) as a result of 
disease progression, relapse, or toxicity. A new line of therapy also starts when a planned period 
of observation off therapy is interrupted by a need for additional treatment for the disease.
Source: Rajkumar 2011, Rajkumar 201536,37

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10.11. Appendix 11:
Formulas for Estimating Glomerular Filtration Rate
Modified Diet in Renal Disease Formula
For creatinine in mg/dL, the estimated glomerular filtration rate (e-GFR) for the MDRD formula is:
e-GFR (MDRD) mL/min per 1.73m2= 175 × [serum creatinine (mg/dL)]-1 154 × [age]-0 203× [1.212 if black]
× [0.742 if female]
For creatinine in μmol/L, the e-GFR for the MDRD formulas is:
e-GFR (MDRD) mL/min per 1.73m2= 175 x [serum creatinine (μmol/L)/88.4]-1 154 × [age]-0 203 × [1.212 
if black] × [0.742 if female]
Source: Levey 200625

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10.12. Appendix 12: Contraceptive and Barrier Guidance and Collection of 
Pregnancy Information
Subjects must follow contraceptive measures as outlined in Section 5.1, Inclusion Criteria. 
Pregnancy information will be collected and reported as noted in Section 8.3.3, Pregnancy and 
Section 10.4 Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-up, 
and Reporting.
Definitions
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below).
Woman Not of Childbearing Potential
!
premenarchal
A premenarchal state is one in which menarche has not yet occurred.
!
postmenopausal
A postmenopausal state is defined as no menses for 24 months without an alternative medical 
cause. A high follicle stimulating hormone level (>40 IU/L or mIU/mL) in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT), however in the absence of 12 months 
of amenorrhea, a single follicle stimulating hormone measurement is insufficient.
!
permanently sterile
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal 
occlusion/ligation procedures, and bilateral oophorectomy.
Note: If the childbearing potential changes after start of the study (eg, a premenarchal woman 
experiences menarche) or the risk of pregnancy changes (eg, a woman who is not heterosexually 
active becomes active), a woman must follow contraception requirements as described throughout
the inclusion criteria.
If reproductive status is questionable, additional evaluation should be considered.
Contraceptive (birth control) use by men or women should be consistent with local regulations 
regarding the acceptable methods of contraception for those participating in clinical studies.
Typical use failure rates may differ from those when used consistently and correctly. Use should 
be consistent with local regulations regarding the use of contraceptive methods for subjects in 
clinical studies.
Because of the embryo-fetal risk of pomalidomide, all subjects treated with PVd or DPd must be 
enrolled in the pomalidomide pregnancy prevention program applicable in their region. 
Investigators should comply with the Global Pomalidomide Pregnancy Prevention Plan or with 
the respective country-specific Pomalyst/Imnovid (pomalidomide) Risk Minimization Program 
(ie, Pregnancy prevention program) as implemented in the post-marketing setting and ensure that 

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all subjects adhere to these programs. When no Pomalyst/Imnovid (pomalidomide) Risk 
Minimization Program exists, subjects must adhere to the Global pomalidomide Pregnancy 
Prevention Plan.
Examples of Contraceptives 
EXAMPLES OF CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE:
USER INDEPENDENT
Highly Effective Methods That Are User Independent Failure rate of <1% per year when used 
consistently and correctly.
!
Implantable progestogen-only hormone contraception associated with inhibition of ovulationb
!
Intrauterine device (IUD)
!
Intrauterine hormone-releasing system (IUS)
!
Bilateral tubal occlusion
!
Vasectomized partner
(Vasectomized partner is a highly effective contraceptive method provided that the partner is the 
sole sexual partner of the woman of childbearing potential and the absence of sperm has been 
confirmed. If not, additional highly effective method of contraception should be used. 
Spermatogenesis cycle is approximately 74 days.)
USER DEPENDENT
Highly Effective Methods That Are User Dependent Failure rate of <1% per year when used 
consistently and correctly.
!
Progestogen-only hormone contraception associated with inhibition of ovulationb
)oral
)injectable
!
Sexual abstinence
(Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the subject.)
NOT ALLOWED AS SOLE METHOD OF CONTRACEPTION DURING THE STUDY (not 
considered to be highly effective - failure rate of ∀1% per year)
!
Progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary 
mode of action.
!
Male or female condom with or without spermicidec
!
Cap, diaphragm, or sponge with spermicide
!
A combination of male condom with either cap, diaphragm, or sponge with spermicide (double-
barrier methods)c
!
Periodic abstinence (calendar, symptothermal, post-ovulation methods)
!
Withdrawal (coitus-interruptus)
!
Spermicides alone
!
Lactational amenorrhea method (LAM)
a) Typical use failure rates may differ from those when used consistently and correctly. Use should be 
consistent with local regulations regarding the use of contraceptive methods for subjects in clinical 
studies.
b) Hormonal contraception may be susceptible to interaction with the study intervention, which may 
reduce the efficacy of the contraceptive method. In addition, consider if the hormonal contraception 
may interact with the study intervention.

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c) Male condom and female condom should not be used together (due to risk of failure with friction).
Pregnancy During the Study
All initial reports of pregnancy in female subjects or partners of male subjects must be reported to 
the sponsor by the study-site personnel within 24 hours of their knowledge of the event using 
appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, spontaneous 
abortion, fetal death, stillbirth, congenital anomalies, and ectopic pregnancy) are considered 
serious adverse events and must be reported using the Serious Adverse Event Form. Any subject
who becomes pregnant during the study must discontinue further study treatment. Because the 
effect of the study treatment on sperm is unknown, pregnancies in partners of male subjects included 
in the study will be reported as noted above. Follow-up information regarding the outcome of the 
pregnancy and any postnatal sequelae in the infant will be required.

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10.15. Appendix 15: Immune Effector Cell-associated Encephalopathy (ICE) Tool
Immune Effector Cell-Associated Encephalopathy (ICE) Toola
Orientation: Orientation to year, month, city, hospital: 
!
4 points
Naming: Name 3 objects (eg, point to clock, pen, button): 
!
3 points
Following commands: (eg, show me 2 fingers or Close your eyes and stick out your tongue): 
!
1 point
Writing: Ability to write a standard sentence (eg, our national bird is the bald eagle): 
!
1 point
Attention: Count backwards from 100 by ten: 
!
1 point
a: ICE-Tool Scoring:
!
Score 10: No impairment
!
Score 7-9: Grade 1 ICANS
!
Score 3-6: Grade 2 ICANS
!
Score 0-2: Grade 3 ICANS
!
Score 0 due to patient unarousable and unable to perform ICE assessment: Grade 4 ICANS

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10.16. Appendix 16: JNJ-68284528 Outpatient Administration Guidelines
When evaluating the suitability for outpatient administration, if allowed by local regulations and 
institutional guidance among other considerations, investigators should assess the subject’s clinical status 
and the health care facility capability to safely manage outpatient logistics. General recommendations for 
each of these considerations are provided below:
1.
Clinical consideration
General guidance for clinical considerations for a subject that is suitable for outpatient administration and 
follow-up includes the following:
)
Not requiring packed red blood cell or platelet transfusions more frequently than every 2 days
)
No presence of an indwelling central line (with the exception of a PICC line) given risk of 
infection in the setting of cytopenia
)
No fever or active infection (bacterial, fungal, viral) since study enrollment
)
No Grade 3 or higher non-hematologic toxicities of cyclophosphamide and fludarabine including 
nausea, vomiting, and diarrhea
)
No clinically significant coagulopathy that would increase the risk of bleeding in the setting of 
cytopenia
)
No high tumor burden defined as at least 60% plasma cell infiltration of the marrow and/or the 
presence of extramedullary disease
)
No risk factors for developing clinically significant tumor lysis syndrome and requiring 
management with increased hydration, allopurinol, or rasburicase. Patients who are receiving 
prophylactic treatment for TLS are eligible for outpatient infusion, if deemed stable by the 
investigator
)
No rapidly progressing disease
)
No deterioration in neurologic status, including mental status changes such as confusion or 
increased somnolence. The only exception is confusion or somnolence that has resolved and must 
be attributed to diphenhydramine premedication for JNJ-68284528.
)
The following laboratory parameters:
o
eGFR of ≥40 mL/min/1.73 m2
o
AST and ALT≤3 times the upper limit of normal
2.
Logistical consideration for qualified healthcare facility
Outpatient administration and post-JNJ-68284528 infusion follow-up must take place at a qualified 
healthcare facility.
The following should be considered for outpatient administration and follow-up until Day 4 prior to 
inpatient admission from Day 5 to Day 14 of JNJ-68284528 infusion:
)
Site must discuss with subjects how to recognize signs of CAR-T toxicities, including CRS and 
neurotoxicity
)
Site must provide patients with educational material including but not limited to emergency 
contact information

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)
Subject will receive daily phone call follow-ups from the hospital site staff (as required by the 
Schedule of Activities Table 5 and Section 10.17) during typical business hours
)
Subject is required to stay within 30 minutes of transportation to the hospital and remain in the 
company of a competent adult at all times until the time of readmission on Day 5 after 
JNJ-68284528 infusion
)
Subject must comply with all the protocol requirement procedures, including measuring and 
recording of body temperature twice per day, and coming to the site for safety assessments 
according to the Schedule of Activities (Table 5).
)
Subject must be made aware of the presenting signs and symptoms of CAR-T associated toxicities 
(including but not limited to CRS, neurotoxicity’s, infections, etc. (as presented in the patient 
wallet card)
)
Admission to the hospital is required at any time in the event of any presenting signs and 
symptoms of CRS and/or neurotoxicity even if these occur before Day 5. Even without symptoms 
of CRS and/or neurotoxicity, subject will be admitted for inpatient monitoring from Day 5 to 
Day 14 of JNJ-68284528 infusion
)
If a subject does not develop symptoms of CRS and/ or neurotoxicity or other clinically significant 
adverse event until Day 10 post JNJ-68284528 infusion, subject may be discharged with daily 
outpatient phone call follow-ups during business hours through study Day 14. Upon discharge 
from the hospital, the subject must stay locally within 1 hour of transportation to the hospital and 
remain in the company of a competent adult at all times for 1 additional week, or up to study 
Day 21, whichever is sooner
)
Subjects that experience CRS and/or neurotoxicity, can be discharged from the hospital when 
they are afebrile for 24 hours and signs and symptoms of CRS and/or neurotoxicity or other 
clinically significant adverse event have resolved

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10.17. Appendix 17: Monitoring for Subjects Receiving JNJ-68284528 as 
Outpatient
Subjects eligible to receive JNJ-68284528 as an outpatient (see recommendations in Section 10.16) in 
consultation with and approval of the sponsor.
Day 1
JNJ-68284528 infusion
Day 1 to 4
! Subject is required to stay within 30 minutes of transportation to the hospital 
and remain in the company of a competent adult at all times
! Subject will receive daily phone call follow-ups from hospital staff during 
typical business hours 
! Admission to the hospital is required at any time in the event of any presenting 
signs and symptoms of CRS and/or neurotoxicity
Day 5 to 14
! Required inpatient admission
! Potential discharge on Day 10 for subjects who do not develop symptoms of 
CRS, neurotoxicity, or other significant adverse events
)
Subjects discharged on Day 10 will receive daily phone call follow-ups 
from the hospital staff during typical business hours through Day 14

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10.18. Appendix 18: The Family of Antihistamine Medications
The following antihistamines may be used for daratumumab pre-injection medication (including, but not 
limited to):
!
Diphenhydramine
!
Cetirizine
!
Fexofenadine
!
Loratadine
!
Clemastine
!
Dexchlorpheniramine
!
Promethazine*
* The IV use of promethazine should be avoided. 

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10.19. Appendix 19: EORTC QLQ-C30

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10.20. Appendix 20: Multiple Myeloma Symptom and Impact Questionnaire
(MySIm-Q)

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10.22. Appendix 22:  Patient’s Global Impression of Severity of Multiple Myeloma
Patient’s Global Impression of Severity (PGIS)
of Multiple Myeloma
Overall, how would you rate the severity of your multiple myeloma disease currently?  
(Please select one response)
 1. None
 2. Mild 
 3. Moderate 
 4. Severe 
 5. Very Severe               
PGIS_CD_v2.0

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10.23. Appendix 23: NCI PRO-CTCAE ITEMS

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10.26. Appendix 26: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents (TOC).

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10.27. Appendix 27: CCI
CCI

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10.28. Appendix 28: Anti-microbial Prophylaxis Recommendations
Subjects should receive antimicrobial prophylaxis as per recommendations below or per 
institutional standards.
Prophylaxis
Therapy 
Start 
Stop 
Anti-Bacterial 
Fluoroquinolones (Levofloxacin –
500 mg PO or IV daily, or equivalent)
Suggested Alternative for subjects with 
allergy to quinolones:
Cefpodoxime - 200 mg PO twice a day
At neutropenia
onset (ANC 
< 500/μL)
Or by Day -1
At Neutropenia 
resolution (for example, 
ANC ≥ 500/μL)
Anti-Fungal
Fluconazole - 400 mg daily
(or equivalent) 
Alternatives: Caspofungin or 
Micafungin
For prolonged neutropenia – Consider 
switching to Posaconazole, or as per 
institutional guidelines
At neutropenia 
onset (ANC 
< 500/μL)
Or by Day -1
At Neutropenia 
resolution (for example, 
ANC ≥ 500/μL)
Anti-Viral
Acyclovir – 400 - 800 mg PO twice a 
day2 (dose to be adjusted as per 
institutional guidelines)
Alternative:
Valacyclovir - 500 mg PO twice a day
By Day -1 of 
infusion
Suggested for at least 
12 months post infusion 
Pneumocystis
Pneumonia (PCP)
Pentamidine (as per institutional 
guidelines) followed by Trimethoprim-
sulfamethoxazole – 1 DS tablet PO 
daily or 1 SS tablet PO daily
Alternatives:
Pentamidine (as per institutional 
guidelines), or
Dapsone – 100 mg PO daily or 50 mg 
PO BID,
or
Atovaquone – 1500 mg PO daily
By Day -1 of 
infusion
Pentamidine (or 
alternative)
Day 28 (or when 
cytopenia recovers)
Trimethoprim-
sulfamethoxazole –
1 DS tablet PO daily 
or 1 SS tablet PO 
daily
Suggested duration: 
6 months post-infusion 
OR until CD4 count 
≥200 cells/μL, 
(whichever is longer)
Consider CMV serology at baseline, monitor with PCR testing as clinically indicated per 
institution guidance

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10.29. Appendix 29: Study Conduct During a Natural Disaster
GUIDANCE ON STUDY CONDUCT DURING THE COVID-19 PANDEMIC
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on 
the conduct of this clinical study due to, for example, self-isolation/quarantine by participants and 
study-site personnel; travel restrictions/limited access to public places, including hospitals; study 
site personnel being reassigned to critical tasks. 
In alignment with recent health authority guidance, the sponsor is providing options for study 
related participant management in the event of disruption to the conduct of the study. This guidance 
does not supersede any local or government requirements or the clinical judgement of the 
investigator to protect the health and well-being of participants and site staff. If, at any time, a 
participant’s safety is considered to be at risk, study intervention will be discontinued, and study 
follow-up will be conducted.
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent 
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each 
contact, participants will be interviewed to collect safety data. Key efficacy endpoint assessments 
should be performed if required and as feasible. Participants will also be questioned regarding 
general health status to fulfill any physical examination requirement. 
Every effort should be made to adhere to protocol-specified assessments for participants on study 
intervention, including follow-up. Modifications to protocol-required assessments may be 
permitted via COVID-19 Appendix after consultation with the participant, investigator, and the 
sponsor. Missed assessments/visits will be captured in the clinical trial management system for 
protocol deviations. Discontinuations of study interventions and withdrawal from the study should 
be documented with the prefix “COVID-19-related” in the case report form (CRF). 
The sponsor will continue to monitor the conduct and progress of the clinical study, and any 
changes will be communicated to the sites and to the health authorities according to local guidance. 
Modifications made to the study conduct as a result of the COVID-19 pandemic should be 
summarized in the clinical study report.
Testing for COVID-19 should be performed according to local guidance. If a subject has tested 
positive for COVID-19, the following should be reported in the EDC tool:
!
all cases of COVID-19, regardless of severity or causality (including asymptomatic 
COVID-19) up to 1 year after cilta-cel infusion
!
all medications given to prevent (including vaccines) or treat COVID-19 up to 1 year after 
cilta-cel infusion

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GUIDANCE SPECIFIC TO THIS PROTOCOL:
These emergency provisions are meant to ensure subject safety on study while site capabilities are 
compromised by COVID-19-related restrictions. As restrictions are lifted and the acute phase of 
the COVID-19 pandemic resolves, sites should revert to original protocol conduct as soon as 
feasible.
Study Visits and Assessments
!
At the discretion of the investigator and with sponsor approval, study visits may be performed 
remotely via telemedicine technology that connects study subjects to their research 
coordinators and investigators. Blood sample collection may be performed at the subject’s 
home by mobile study personnel (ie, nurses and mobile phlebotomist), if not using the 
sponsor’s home health nursing solution. Home health nursing can be done via site contract 
with a visiting nurse service independent of the sponsor, if not using the sponsor’s home health 
nursing solution. Patient reported outcome questionnaires can be completed by telephone or 
during the home health visit.
!
For subjects who are unable to come to the site for scheduled visits and/or if site capabilities 
are compromised by COVID-19-related restrictions, contact (eg, telephone, videoconference, 
or other channels) with the subject should be made in advance, to collect information on the 
subject’s current health status and any new or ongoing adverse events and concomitant 
medications. Normal study procedures should be followed for the applicable visits as closely 
as possible even if lab assessments and physical exams are performed locally. Where local 
laboratories are used, it is important to ensure appropriate documentation of laboratory 
reference ranges. The remote contact with the subject (as allowable per local regulations), the 
local laboratory results, and the sponsor discussion should be documented in the subject 
source record. Similarly, at a minimum, a comment must be entered in the Comments eCRF 
clearly designating as “COVID-19-related” and acknowledging the discussion between the 
investigator and the sponsor.
!
All deviations from protocol-required assessments should be documented in detail within the 
subject’s source record and should be clearly designated as “COVID-19-related”. It must be 
documented if a visit is conducted remotely. Source documentation should detail how each 
assessment was collected (eg, remote vs. on-site, central vs. local laboratory, vital signs taken 
at home by caretaker vs. delegated in-home nursing).
!
Consenting and re-consenting of subjects will be performed as applicable for the measures 
taken (including also remote consenting by phone or video consultation) and according to 
local guidance for informed consent applicable during the COVID-19 pandemic.
The above measures are recommended for consideration on a temporary basis during the 
COVID-19 pandemic to ensure that subject assessments continue as outlined in the protocol 
without imposing health risk to subjects, their families, and site staff. Every effort should be made 
to complete all protocol-required assessments. 

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GUIDANCE ON COVID-19 VACCINE TIMING, AND COVID-19 PREVENTION AND 
TREATMENT FOR CILTA-CEL RECIPIENTS
It is recommended that participants receive prophylactic COVID-19 vaccination when locally 
available, at the discretion of investigator judgement or institutional practice, and in compliance 
with the cilta-cel study protocol and local labels for the vaccine. Below is general guidance for 
consideration.
Many vaccines against COVID-19 are being developed with different technologies and platforms 
and may have safety and efficacy profiles that are not fully characterized even after preliminary 
health authority approval. However, the benefit-risk ratio of receiving a COVID-19 vaccine among 
patients with multiple myeloma participating in cilta-cel studies is considered to be positive and 
should be considered for administration while in compliance with the cilta-cel study protocol and 
when not otherwise contraindicated for use in the vaccine label.
Per protocol, live attenuated vaccines must be completed at least 6 weeks prior to lymphodepletion 
therapy or initiated at least 112 days after cilta-cel infusion. There are no specific timing 
restrictions for inactivated vaccines, which include vaccines which use alternative technology like 
mRNA or replication-incompetent viral vectors, per protocol. Enrollment into an interventional 
clinical trial for an experimental vaccine is prohibited during study. Any vaccination, including 
COVID-19 vaccinations, must be recorded on the Concomitant Medication page of the eCRF. 
No data is currently available to suggest that COVID-19 vaccines pose specific or additional safety 
risk beyond other vaccines for cancer patients undergoing treatment. Theoretically, a diminished 
immune response may occur in immunocompromised patients, and therefore these patients may 
have reduced vaccine effectiveness.
While not specifically required per protocol, it is encouraged to complete the COVID-19 vaccine 
series at least 2 weeks prior to lymphodepletion, and to delay vaccination for at least 3 months 
after cilta-cel infusion, to maximize immune response.
Several organizations and journals have published recommendations for COVID-19 vaccine 
administration in cancer patients, including:
!
European Society for Blood and Marrow Transplantation (EBMT)
https://www.ebmt.org/covid-19-and-bmt 
!
American Society for Transplantation and Cellular Therapy (ASTCT) 
https://www.hematology.org/covid-19/ash-astct-covid-19-vaccination-for-hct-and-car-t-cell-
recipients
!
National Comprehensive Cancer Network (NCCN) 
https://www.nccn.org/covid-19/pdf/COVID-19_Vaccination_Guidance_V2.0.pdf
!
Centers for Disease Control and Prevention (CDC)
https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html

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!
Nature Reviews Clinical Oncology: COVID-19 vaccine guidance for patients with cancer 
participating in oncology clinical trials. Desai A, Gainor JF, Hegde A, et al. (March 15, 2021). 
DOI: 10.1038/s41571-021-00487-z
https://www.nature.com/articles/s41571-021-00487-z
Investigators should inform patients that emerging data show that patients receiving cilta-cel are 
possibly at higher risk of severe/fatal outcomes from COVID-19 infection compared with patients 
receiving standard of care therapy (Section 6.1.6.7).
Based on guidance from the organizations listed above, the following measures should be 
implemented to minimize subjects’ risk of severe COVID-19 infection: 
!
Subjects, particularly those who are less than 6 to 9 months from cilta-cel infusion, should be 
reminded that the ongoing pandemic is still putting them at risk of contracting COVID-19.
Investigators should ask subjects to continue to limit their risk of exposure to infected 
individuals as much as possible and strictly adhere to prevention measures such as proper 
masking, hand hygiene, social distancing, and avoiding travel and public transportation to the 
extent possible.
!
Investigators should discuss with subjects the importance of COVID-19 vaccines in the 
prevention of severe illness, hospitalization, and death from COVID-19. Subjects should 
assume that any vaccination administered prior to lymphodepletion and cilta-cel infusion no 
longer provides protection. For this reason, it is strongly recommended that all subjects 
receive a full COVID-19 vaccination series (eg, a primary series of 3 vaccines and a 4th 
booster dose for mRNA vaccines; note: mRNA vaccines are recommended), no sooner than 
3 months after cilta-cel infusion, regardless of vaccination status prior to cilta-cel. In addition, 
if not already vaccinated, caregivers, family, and household contacts should be advised to 
receive COVID-19 vaccination as well.
!
Investigators should consider prophylaxis (eg, Evusheld, if available in the region) to reduce 
subjects’ risk of severe/fatal COVID during the first 6 to 9 months after cilta-cel. It is critical 
that subjects understand that multiple myeloma patients (even those who have not received 
CAR-T therapy) may not seroconvert until after the 3rd vaccine dose and as a result they may 
remain at a very high risk of severe COVID-19 for at least 2 to 3 months after starting 
vaccination.2
!
Investigators should instruct subjects to notify them or study site staff immediately if they are 
diagnosed with COVID-19, even if they are asymptomatic, so that appropriate treatment 
measures can be determined.
!
If available in the region, antivirals (eg, Paxlovid or other available agents) should be 
considered early after COVID-19 diagnosis. Subjects may remain asymptomatic or have 
minimal symptoms for a period of time prior to deteriorating. Investigators should make
subjects aware that these drugs may potentially significantly lower their risk of severe 
COVID-19.

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SAEs (regardless of 
causality) for 
duration of study.
!
≥Grade 3 CRS
!
≥Grade 3 Neurotoxicity
!
Any grade movement and neurocognitive toxicity (ie, parkinsonism)
!
SPMs (any grade)
a
Expedited reporting includes reporting to Sponsor Global Medical Safety within 24 hours via SAE Fax Form or 
other defined SAE reporting process per protocol.

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11.
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