Comparative Effectiveness of Elranatamab (PF 06863135) in Clinical Study C1071003 Versus Standard of Care (SOC) in Real-World (RW) External Control Arms in Patients With Triple-Class Refractory (TCR) Multiple Myeloma (MM)
Conditions: Multiple Myeloma
Sponsor: Pfizer

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NON-INTERVENTIONAL (NI) STUDY PROTOCOL
Study Information
Title
Comparative Effectiveness of Elranatamab
(PF-06863135) in Clinical Study C1071003 Versus 
Standard of Care (SOC) in Real-World (RW)
External Control Arms in Patients with Triple-Class 
Refractory (TCR) Multiple Myeloma (MM)
Protocol number
C1071024
Protocol version identifier
1.0
Date
15 August 2022
Active substance
Elranatamab (PF-06863135)
Research question and objectives
Primary objective:
1. To compare the objective response rate 
(ORR) among TCR MM patients treated with 
elranatamab in Study C1071003 with a 
comparable cohort of TCR MM patients 
receiving SOC therapy within external 
comparator arms.
Secondary objectives:
1. To compare time to treatment response 
(TTR) in TCR MM patients treated with 
elranatamab in Study C1071003 with a 
comparable cohort of TCR MM patients 
receiving SOC therapy.
2. To compare the duration of response (DOR) 
in TCR MM patients treated with 
elranatamab in Study C1071003 with a 
comparable cohort of TCR MM patients 
receiving SOC therapy.

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Author
, PhD
 
This document contains confidential information belonging to Pfizer.  Except as otherwise agreed to in 
writing, by accepting or reviewing this document, you agree to hold this information in confidence and not 
copy or disclose it to others (except where required by applicable law) or use it for unauthorized purposes.  In 
the event of any actual or suspected breach of this obligation, Pfizer must be promptly notified.
PPD
PPD

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1. TABLE OF CONTENTS
1. TABLE OF CONTENTS.......................................................................................................3
2. LIST OF ABBREVIATIONS................................................................................................5
3. RESPONSIBLE PARTIES....................................................................................................7
4. ABSTRACT...........................................................................................................................8
5. AMENDMENTS AND UPDATES.......................................................................................9
6. MILESTONES.....................................................................................................................10
7. RATIONALE AND BACKGROUND................................................................................11
8. RESEARCH QUESTION AND OBJECTIVES .................................................................13
9. RESEARCH METHODS ....................................................................................................13
9.1. Study design ............................................................................................................13
9.2. Setting......................................................................................................................15
9.2.1. Study C1071003 .........................................................................................15
9.2.2. Real-world data sources..............................................................................16
9.2.3. Inclusion and exclusion criteria for external control arms .........................17
9.3. Variables..................................................................................................................20
9.4. Data sources ............................................................................................................24
9.5. Study size ................................................................................................................25
9.6. Data management....................................................................................................25
9.7. Data analyses...........................................................................................................25
9.7.1. Descriptive statistics...................................................................................26
9.7.2. Primary analyses.........................................................................................27
9.7.3. Sensitivity analyses.....................................................................................28
9.8. Quality control.........................................................................................................29
9.9. Limitations of the research methods .......................................................................29
9.10. Other aspects .........................................................................................................29
10. PROTECTION OF HUMAN SUBJECTS ........................................................................30
10.1. Patient information................................................................................................30
10.2. Patient consent.......................................................................................................30
10.3. Patient withdrawal.................................................................................................30
10.4. Institutional review board (IRB)/ Independent ethics committee (IEC)...............30

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10.5. Ethical conduct of the study..................................................................................30
11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................30
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........30
13. REFERENCES ..................................................................................................................31
14. LIST OF TABLES.............................................................................................................34
15. LIST OF FIGURES ...........................................................................................................35
16. APPENDIX........................................................................................................................36
16.1. Appendix. Inclusion and exclusion criteria in Study C1071003, Flatiron 
Health and COTA......................................................................................................36
17. ANNEX 1. LIST OF STAND ALONE DOCUMENTS ...................................................48

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2. LIST OF ABBREVIATIONS
Abbreviation
Term
ADC
Antibody-drug conjugate
AE
Adverse Event
Anti-CD38
Anti-CD38 monoclonal antibodies
AIPW
Augmented Inverse Probability Weights
ATE
Average Treatment Effect
AST
Aspartate Aminotransferase
ALT
Alanine Aminotransferase
BCMA
B-Cell Maturation Antigen
BM
Bone Marrow
CAR
Chimeric Antigen Receptor
CI
Confidence Interval
CR
Complete Response
DOR
Duration of Response
ECOG
Eastern Cooperative Oncology Group
EHR
Electronic Health Record
EMA
European Medicines Agency
FDA
Food and Drug Administration
FLC
Free Light Chain
GBS
Guillain-Barre Syndrome
GVHD
Graft Versus Host Disease
HBV
Hepatitis B Virus
HCV
Hepatitis C Virus
HIV
Human Immunodeficiency Virus
IMiD
Immunomodulatory Drug
IMWG
International Myeloma Working Group
IPTW
Inverse Probability of Treatment Weights
KarMMa-RW
Comparison of Idecabtagene Vicleucel with Real-World Outcomes in 
Relapsed and Refractory Multiple Myeloma
LVEF
Left Ventricular Ejection Fraction
LOT
Line of Therapy
MAMMOTH
Monoclonal Antibodies in Multiple Myeloma: Outcomes after Therapy 
Failure
MM
Multiple Myeloma
M-protein
Monoclonal immunoglobulin protein
MUGA
Multigated acquisition scan
NI 
Non-Interventional
OR
Objective Response
ORR
Objective Response Rate 
OS
Overall Survival
PD
Progressive Disease

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Abbreviation
Term
PI
Proteasome Inhibitor
PFS
Progression-Free Survival
POEMS
Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal 
Gammopathy, and Skin Changes
PR
Partial Response
PS
Propensity Scores
QT
Time from the beginning of the QRS Complex to the End of the T Wave
QTcF
Corrected QT (Fridericia Method)
RW
Real-World
RWD
Real-World Data
RRMM
Relapsed/Refractory Multiple Myeloma
SAP
Statistical analysis plan
SARS-Cov2
Severe Acute Respiratory Syndrome- Coronavirus 2
sCR
Stringent Complete Response 
SMD
Standardized Mean Difference
SOC
Standard of Care
SPEP
Serum Protein Electrophoresis
TCR
Triple-Class Refractory
TTR
Time to Treatment Response
ULN
Upper Limit of Normal
UPEP
Urine Protein Electrophoresis 
US
United States
VGPR
Very Good Partial Response 

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3. RESPONSIBLE PARTIES
Principal Investigator(s) of the Protocol
Name, degree(s)
Job Title
Affiliation
Address
 PhD
 
 
 
, MPH
 
, MD, PhD
 
, PharmD, MBA
 
 
, PhD
, MPH
, MD, MPH
 
, MPH
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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4. ABSTRACT
Not applicable

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5. AMENDMENTS AND UPDATES
None

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6. MILESTONES
                                  Milestone
Planned date
Start of data collection
03 October 2022
End of data collection
16 October 2022
Final study report
11 December 2022

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7. RATIONALE AND BACKGROUND
MM is a rare and progressive type of cancer that is characterized by the rapid accumulation 
of monoclonal plasma cells in the bone marrow (BM). This results in the production of 
monoclonal immunoglobulin protein (M-protein) and eventually leads to end-organ damage. 
The global incidence of MM is rising and is estimated at 160,000 in 2018, with 106,000 
deaths attributed to MM annually. In the past 3 decades, from 1990 to 2016, the global 
incidence of MM has increased by 126%, with the highest incidence rates reported in 
Australia, Western Europe, and the United States (US)(Padala et al., 2021).
Over the years, advancements have been made in the discovery and utilization of MM 
therapies, with current SOC including proteasome inhibitors (PIs) (bortezomib, carfilzomib, 
ixazomib), immunomodulatory drugs (IMiD) (thalidomide, lenalidomide, pomalidomide) and 
anti-CD38 monoclonal antibodies (anti-CD38: daratumumab and isatuximab)(Wallington-
Beddoe and Pitson, 2017).
Despite these treatment advances, a major proportion of MM patients will fail all 3 classes of 
the current SOC regimens (including PI, IMIDs, and anti-CD38) and become triple class 
refractory (TCR). The treatment of TCR MM presents a therapeutic challenge because of the 
inherent clonal heterogeneity and genetic instability of MM tumor cells, influencing the 
eventual development of therapeutic resistance (Nooka et al., 2015) . Therefore, as TCR 
patients progress and are exposed to an increasing number of therapies, the duration of 
response (DOR) decreases along with overall survival (OS) until the disease is ultimately 
fatal (Yong et al., 2016).
Pfizer has developed elranatamab (PF-06863135), an investigational B-cell maturation 
antigen (BCMA) CD3-targeted bispecific antibody, for the treatment of patients with TCR 
MM. Belantamab mafodotin-blmf was the first BCMA therapy approved by the FDA, in 
August 2020. The preliminary results of the Phase 1 study (NCT03269136) demonstrated 
manageable safety of elranatamab and a response rate of 69% (ie, 9/13 patients) at the 
recommended dose of 1000 µg/kg (Sebag et al., 2022). Additionally, elranatamab has been 
granted Fast Track Designation by the US Food and Drug Administration (FDA) and 
European Medicines Agency (EMA) to aid the rapid development and review of this novel 
agent and thereby address the unmet medical needs of TCR MM patients (Pivotal Phase 2 
MagnetisMM-3 Trial| Pfizer, 2022). Pfizer is currently conducting a Phase 2 study to 
evaluate the clinical benefit of elranatamab in TCR MM patients (Study C1071003). 
Considering the ethical and practical challenges associated with conducting a randomized 
clinical trial within a particularly difficult-to-treat population of MM patients with unmet 
needs and no clear single SOC, a single arm design was adopted for the Phase 2 study (First 
Data from Planned Interim Analysis of Pivotal Phase 2 MagnetisMM-3 Trial | Pfizer, 2022). 
Thus, there is a need to generate evidence on the clinical outcomes of TCR patients who 
receive SOC to help contextualize the results from Study C1071003. This will be 
accomplished by creating an external control arm using Real-World Data (RWD) to support 
the ongoing evaluation of elranatamab.
Previous RW studies have provided data on clinical outcomes in patients with 
relapsed/refractory MM (RRMM) using RWD. In the MAMMOTH study (Gandhi et al., 

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2019), 275 patients from 14 academic institutions were identified in the US with a diagnosis 
of active MM who were refractory to anti-CD38, daratumumab, or isatuximab, administered 
as monotherapy or in combination. Median OS from the time when patients were refractory 
to an anti-CD38 was 8.6 months (95% confidence interval, CI: 7.5 - 9.9). The ORR to the 
first regimen after patients became refractory to anti-CD38 was 31% and the median 
progression-free survival (PFS) and OS in patients in the same group were 3.4 and 
9.3months, respectively.
The KarMMa-RW study was a global NI, retrospective study that assessed treatment patterns 
and outcomes in RW RRMM patients treated with currently available therapies, and whose 
characteristics were similar to the KarMMa study, a Phase 2 single-arm study of 
idecabtagene vicleucel in heavily pretreated RRMM patients who were triple-class exposed 
and refractory to the last regimen (Jagannath et al., 2020). Approximately 43% of the 
KarMMa-RW population were TCR. The ORR of the 190 eligible RRMM patients in the 
RW setting was 32% (95% CI: 24.4 - 42.3), and 29% in the matched adjusted eligible 
RRMM subset. In the eligible RRMM cohorts, the median PFS was 3.5 months, and the 
median OS was 14.7 (95% CI: 14.0-15.4) months.
Regulatory Agencies, including FDA and EMA, have recognized the utility of external 
control arms derived from RWD in decision making, and have established guidance on 
conditions that should be satisfied before an external control approach is deemed appropriate, 
as well as key methodological considerations (EMA, 2001; FDA, 2018; FDA, 2019). 
According to these guidelines, an external control approach is considered appropriate under 
certain conditions, including(a) there is a high unmet need (eg, serious rare diseases), (b) 
there is a well-documented, highly predictable disease course that can be objectively 
measured and verified, and (c) there is an expected drug effect that is large, self-evident, and 
temporally closely associated with the intervention (CHMP, 2002; Jahanshahi et al., 2021).
This study aims to compare the ORR, TTR, and the DOR in patients from Study C1071003 
treated with elranatamab versus RW TCR MM patients treated with SOC. To reduce the 
potential for bias, external control arms will be constructed by selecting fit-for-purpose RW 
data (RWD) sources (ie, reliable and relevant)(FDA, 2018), appropriate comparative 
effectiveness methods, and robust statistical techniques (eg, inverse probability of treatment 
weighting [IPTW]) (Carroll, 2016; Ghadessi et al., 2020; Chesnaye et al., 2022).

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8. RESEARCH QUESTION AND OBJECTIVES
This study aims to assess the comparative effectiveness of elranatamab versus SOC treatment
in TCR MM patients using external control arms for the open-label, multicenter, non-
randomized single-arm Phase 2 Study C1071003.
Primary objective:
To compare ORR among TCR MM patients treated with elranatamab in Study C1071003 
with a comparable cohort of TCR MM patients receiving SOC therapy within external 
comparator arms.
Secondary objectives:
1. To compare TTR in TCR MM patients treated with elranatamab in Study C1071003 
with a comparable cohort of TCR MM patients receiving SOC therapy within 
external comparator arms.
2. To compare DOR in TCR MM patients treated with elranatamab in Study C1071003 
with a comparable cohort of TCR MM patients receiving SOC therapy within 
external comparator arms.
9. RESEARCH METHODS
9.1. Study design
This retrospective cohort study builds upon 2 previous studies, which identified 2 cohorts of 
RW TCR MM patients to use as external control arms for Study C1071003. The cohorts were 
identified from 2 of the US-based oncology electronic health record (EHR) databases, 
Flatiron Health, and COTA (see relating study protocols in ANNEX 1. LIST OF STAND 
ALONE DOCUMENTS). In the current study, 2 external arms will be constructed from 
these 2 cohorts of RW TCR MM patients to maximize comparability to patients from Study 
C1071003 (see Section 9.2.3 for more detail).
MM patients eligible for selection into external control arms will be those patients who are 
refractory to at least 1 PI, 1 IMiD, and 1 anti-CD38, and have started at least 1 new treatment
since documentation of TCR status. Refractory is defined as having disease progression,
according to International Myeloma Working Group (IMWG) criteria or clinical assessment,
while on therapy or within 60 days of the last dose in any line of therapy (LOT), regardless 
of response. However, if a subsequent LOT is initiated and a progression is observed after at 
least 30 days of the LOT start, the patient will be considered refractory to the subsequent 
LOT even if the progression occurred within 60 days after the last dose of the preceding 
LOT. Details on the operational definitions of IMWG criteria for progression used in Flatiron 
and COTA, and a side-by-side comparison with the criteria used in Study C1071003 are 
provided in the relating study protocols in the APPENDIX.
In the RW setting, no single SOC currently exists for TCR MM patients, and combinations of 
treatments are frequently used in lieu of monotherapy (Mikhael, 2020). For simplicity, in this 
protocol, the term “SOC” refers to all standard treatment options available for TCR MM 
patients. Selection of TCR MM patients initiating a new treatment in the external control arm 

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enables comparability of patients at a similar stage in disease progression following TCR 
documentation.
The date of initiation of the first regimen after TCR MM eligibility will be defined as the
index date. Only patients with an index date occurring between 16 November 2015, and 31
March 2022 will be selected (the first anti-CD38 therapy was approved by the FDA on 16
November 2015). The study period will be comprised of the baseline period (time preceding 
the index date) and the observational period (time following the index date). The 
observational period will span from the index date to the earliest of death, or the latest 
available patient’s record, whichever comes first. Clinical outcomes of interest will be ORR,
TTR, and DOR.
For the primary analyses, differences in baseline and key covariate characteristics including 
treatment history and disease-related characteristics at the index date between patients in 
Study C1071003 and each external control arm will be balanced using IPTW (see Section
9.7.2).
Sensitivity analyses will be conducted to evaluate the effect via doubly robust estimation 
using augmented inverse probability weights (AIPW), alternative inclusion/exclusion criteria,
and, if feasible, to evaluate any differences in the magnitude of treatment effect in patients 
with and without prior exposure to BCMA-directed therapy (see in Section 9.7.3).
Finally, a quantitative bias analysis (nullification analysis) will be performed to evaluate the 
robustness of results in the presence of potential threats to internal validity see Section 9.7.3).
A schematic figure of Study C1071003 and external control arms is provided in Figure 1 and 
Figure 2, respectively.

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Figure 1. Baseline and observation periods in Study C1071003
Figure 2. Baseline and observation periods in external control arms
9.2. Setting
9.2.1. Study C1071003 
Study C1071003 is an open-label, multi-center, non-randomized Phase 2 study of 
elranatamab (PF-06863135) monotherapy, which was initiated in February 2021 (Pfizer, 

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2021). To determine the effects of prior BCMA-directed therapy on the response to 
elranatamab monotherapy, Study C1071003 enrolled 2 independent and parallel cohorts, 1
with patients who are naïve to BCMA-directed therapies (Cohort A; approximately 120 
patients) and the other with patients previously exposed to BCMA-directed therapy (Cohort 
B; approximately 60 patients).
9.2.2. Real-world data sources
The cohorts of RW TCR MM patients for the external control arm were previously extracted 
from Flatiron Health and COTA databases that collect information on MM patients treated 
across the US. Flatiron and COTA have been selected according to data availability and as 
fit-for-purpose for fulfilling study objectives (the US FDA, 2018 Framework). The dates for 
the study periods for each RW database have been selected to align as closely as possible to 
each other and to Study C1071003 which will include at least 9 months of follow-up.
Flatiron Health
The Flatiron Health database is a longitudinal, demographically, and geographically diverse 
database derived from EHR data. Flatiron includes data from over 280 community cancer 
centers and academic institutions (~800 sites of care) representing more than 2.4 million 
active the US cancer patients available for analysis. The source population is the overall 
population reported in the EHR and includes patients managed in at least 1 of the US 
oncology centers taking part in the Flatiron Health network from 01 January 2011 onwards.
Flatiron Health databases consist of longitudinal data on MM patients, including normalized 
data from structured EHR, enhanced data on patients’ characteristics abstracted from 
unstructured EHR, and derived data that is created based on Flatiron-specific business rules 
(Flatiron Health, 2021).
Structured data include information on patients’ demographics, visit dates, diagnoses, vitals, 
medications, the Eastern Cooperative Oncology Group (ECOG) performance status, and 
laboratory tests. Unstructured data contain additional information on comorbidities, 
biomarker reports, and details of transplants. Flatiron Health also provides derived data such 
as progression and response variables where algorithms are developed following adapted 
IMWG criteria to identify these events throughout the course of a patients’ journey.
Details on the identification of the external control arm using Flatiron Health data can be 
found in the related protocol as Document 001 in ANNEX 1. LIST OF STAND ALONE 
DOCUMENTS.
COTA
COTA maintains a multidisciplinary data curation approach. The COTA database is a 
longitudinal database derived from the EHR of healthcare provider sites including academic 
institutions, community centers, and hospital systems representing 500,000 patients from 
over 200 sites of care in the US. Data elements are standardized across sources and 
ontologies to create a single, structured dataset to cover the full longitudinal history of a 
patient’s clinical care. For each patient, the datasets contain information from the time of 
initial MM diagnosis to the most recent documentation in the EHR. Patients with insufficient 

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documentation or those having significant gaps in their patient history in the EHR are 
excluded from COTA datasets (COTA,2022).
As with Flatiron Health, COTA collects information from structured and unstructured data 
sources. Derived data based on adapted IMWG criteria are also provided (eg, disease 
progression and treatment response). COTA differs from Flatiron Health in the provision of 
specific databases that are dedicated to reporting factors relevant to the experience of a 
patient with MM and includes datasets containing abstracted information on bone lesions, 
plasmacytomas, radiation therapy, and adverse events (AE).
Details on the identification of the external control arm using COTA data can be found in the 
related protocol as Document 002 in ANNEX 1. LIST OF STAND ALONE DOCUMENTS.
9.2.3. Inclusion and exclusion criteria for external control arms
Comparability of patients between Study C1071003 and the external control arms is 1 of the 
key considerations to minimize bias. Care will be taken to ensure that patients identified from 
each RW TCR MM cohort are similar to the Study C1071003 patients by satisfying pre-
specified inclusion and exclusion criteria. Inclusion and exclusion criteria from Study
C1071003 are provided in Table 1 and will be modified for each cohort of RW TCR patients 
based on data availability. Operational definitions of inclusion and exclusion criteria for each 
RWD source are summarized in the APPENDIX.
Due to the missingness present within RWD sources, there is an inherent tradeoff between 
analyzable sample size and the degree of comparability of patients from Study C1071003
with the external control arm sample. In other words, the more closely the
inclusion/exclusion criteria for the external control arms are aligned to Study C1071003, the 
smaller the available sample size. From each cohort of RW TCR MM patients, we will 
establish 2 samples of external control arms (“critical eligibility criteria” sample and 
“expanded eligibility criteria” sample). Both samples will incorporate the inclusion/exclusion 
criteria from Study C10701003 which represent key clinical variables to define the cohort. 
However, 1 of the samples (“expanded eligibility criteria”) will also incorporate additional 
inclusion/exclusion criteria from Study C1071003 (eg, lab values) at the expense of a smaller 
sample size. 
The critical eligibility criteria sample will constitute the primary analysis set. Sensitivity 
analyses will be conducted using the expanded eligibility criteria to assess the potential 
influence of the selection process on the observed effects (ie, primary analyses will be 
repeated using this sample). The number of patients included/excluded at each step of the 
study will be reported.
For all samples, patient selection into the TCR MM external control arm will include:
1. Having a diagnosis of MM (identified previously).
2. Those who are refractory to at least 1 PI, 1 IMiD, and 1 anti-CD38 treatment (TCR 
MM). Refractory is defined as having disease progression, IMWG criteria or clinical 
assessment, while on therapy or within 60 days of the last dose (if the duration of a 

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subsequent LOT is ≤ 30 days at the time of reported disease progression) in any line, 
regardless of response (identified previously).
3. Patients start at least 1 treatment following their TCR eligibility. The index date will 
be defined as the date of initiation of the first regimen post-TCR MM eligibility.
4. Those having measurable disease according to IMWG criteria (Rajkumar et al., 
2014), ECOG performance status ≤2, and aged 18 years and older at index date.
A tabular view summarizing the inclusion and exclusion criteria of Study C1071003 which 
are available and applied for RW patients is provided in Table 1 (signified with a checkmark 
symbol where the critical and/or expanded selection criteria definitions are applicable).
Table 1. Inclusion and Exclusion criteria for Study C1071003, Flatiron Health, and 
COTA
Patient criteria per Study C1071003
Implementation in 
Flatiron Health
Implementation in 
COTA
Critical
Expanded
Critical
Expanded
Inclusion Criteria
Male or female patients age ≥18 years
ü
ü
ü
ü
Willing and able to comply with all scheduled visits, treatment plans, 
laboratory tests, lifestyle considerations, and other study procedures
X
X
X
X
Prior diagnosis of MM as defined according to IMWG criteria (Rajkumar 
et al, 2014)
ü
ü
ü
ü
Measurable disease, based on IMWG criteria as defined by at least 1 of 
the following
a) Serum M-protein ≥0.5 g/dL by SPEP
b) Urinary M-protein excretion ≥200 mg/24 hours by Urine Protein 
Electrophoresis (UPEP)
c) Serum immunoglobulin Free Light Chain (FLC)≥10 mg/dL (≥100 
mg/L) and abnormal serum immunoglobulin kappa to lambda FLC ratio 
(<0.26 or >1.65)
ü
ü
ü
ü
Patients are TCR defined as being refractory to all 3 of the following:
a) Refractory to at least 1 IMiD
b) Refractory to at least 1 PI
c) Refractory to at least 1 anti-CD38 antibody
Relapsed/refractory to last anti-MM regimen
ü
ü
ü
ü
Initiated at least 1 anti-MM systemic therapy after becoming TCR 
eligible. The first systemic treatment initiation after becoming TCR 
eligible must not comprise any study or investigational agent.*
ü
ü
ü
ü
ECOG performance status ≤2
ü
ü
ü
ü
Adequate hepatic function characterized by all of the following:
a) Total bilirubin ≤2 x Upper Limit of Normal (ULN) (≤3 x ULN if 
documented Gilbert’s syndrome)
b) aspartate aminotransferase (AST) ≤2.5 x ULN
c) alanine aminotransferase (ALT) ≤2.5 x ULN
X
ü
X
ü
Adequate renal function, defined by an 
estimated creatinine clearance ≥30 mL/min (according to the Cockcroft 
Gault formula, by 24-hour urine collection for creatinine clearance, or 
according to the local institutional standard method)
X
ü
X
ü

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Table 1. Inclusion and Exclusion criteria for Study C1071003, Flatiron Health, and 
COTA
Patient criteria per Study C1071003
Implementation in 
Flatiron Health
Implementation in 
COTA
Critical
Expanded
Critical
Expanded
Adequate BM function characterized by all of the following
a) Absolute neutrophil count ≥1.0 × 109/L (use of granulocyte-colony 
stimulating factors is permitted if completed at least 7 days before 
planned start of dosing)
b) Platelets ≥25 × 109/L (transfusion support is permitted if completed 
at least 7 days before the planned start of dosing)
c) Hemoglobin ≥8 g/dL (transfusion support is permitted if completed at 
least 7 days before the planned start of dosing)
X
ü
X
ü
Left ventricular ejection fraction ≥40% as determined by a multigated 
acquisition scan (MUGA) or echocardiogram
X
X
X
X
Resolved acute effects of any prior therapy to baseline severity or 
Common Terminology Criteria for AE Grade ≤1
X
X
X
X
Exclusion Criteria
Active plasma cell leukemia
ü
ü
ü
ü
Amyloidosis
ü
ü
ü
ü
Previous treatment with an anti-BCMA bispecific antibody.
X
X
X
X
Previous administration with an investigational drug within 30 days (or as 
determined by the local requirement) or 5 half-lives preceding the first 
dose of study intervention used in this study (whichever is longer).
ü
ü
ü
ü
Smoldering MM
ü
ü
ü
ü
Stem cell transplant within 12 weeks before enrolment or active Graft 
Versus Host Disease (GVHD).
ü
ü
ü
ü
Any other active malignancy within 3 years before enrolment, except for 
adequately treated basal cell or squamous cell skin cancer, or carcinoma 
in situ.
ü
ü
ü
ü
POEMS syndrome
X
X
X
X
Impaired cardiovascular function or clinically significant cardiovascular 
diseases, defined based on the history of any of the following conditions 
within 6 months before enrolment:
a) Acute myocardial infarction or acute coronary syndromes (eg, 
unstable angina, coronary artery bypass graft, coronary angioplasty or 
stenting, symptomatic pericardial effusion)
b) Clinically significant cardiac arrhythmias (eg, uncontrolled atrial 
fibrillation or uncontrolled paroxysmal supraventricular tachycardia)
c) Thromboembolic or cerebrovascular events (eg, transient ischemic 
attack, cerebrovascular accident, deep vein thrombosis, or pulmonary 
embolism)
d) Prolonged Time from the beginning of the QRS Complex to the End 
of the T Wave (QT) syndrome (or triplicate average Corrected QT 
(Fridericia Method) (QTcF) >470 msec).
X
ü
X
ü
Active Hepatitis B Virus (HBV), hepatitis C virus Hepatitis C Virus 
(HCV), Severe Acute Respiratory Syndrome- Coronavirus 2 (SARS-
CoV2), known Human Immunodeficiency Virus (HIV), or any active, 
uncontrolled bacterial, fungal, or viral infection. Active infections must be 
resolved at least 14 days before enrolment.
ü
ü
ü
ü

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Table 1. Inclusion and Exclusion criteria for Study C1071003, Flatiron Health, and 
COTA
Patient criteria per Study C1071003
Implementation in 
Flatiron Health
Implementation in 
COTA
Critical
Expanded
Critical
Expanded
Other surgical (including major surgery within 14 days prior to 
enrolment), medical, or psychiatric conditions including recent (within the 
past year) or active suicidal ideation/behavior or laboratory abnormality 
that may increase the risk of study participation or, in the investigator’s 
judgment, make the patient inappropriate for the study.
X
X
X
X
Ongoing Grade ≥2 peripheral sensory or motor neuropathy.
X
ü
X
X
History of any grade peripheral sensory or motor neuropathy with prior 
BCMA-directed therapy (Cohort B).
X
ü
X
ü
History of Guillain-Barre Syndrome (GBS) or GBS variants, or history of 
any Grade ≥3 peripheral motor neuropathy
X
ü
X
X
Investigator site staff or Pfizer employees directly involved in the conduct 
of the study, site staff otherwise supervised by the investigator, and their 
respective family members.
X
X
X
X
Known or suspected hypersensitivity to the study intervention or any of its 
excipients.
X
X
X
X
Live attenuated vaccine must not be administered within 4 weeks of the 
first dose of the study intervention.
X
X
X
X
Note:
* This criterion is not among the inclusion/exclusion criteria of Study C10710003 and is applied only to RW patients.
9.3. Variables
Exposure definition
In each comparison, patients will be classified into one of the two treatment groups according 
to the therapy received after TCR eligibility, as those treated with elranatamab and those 
treated with a SOC regimen (any standard treatment option available for RW TCR MM 
patients).
If feasible based on data availability, patients from elranatamab and SOC treatment groups 
will further be classified into those with and without exposure to BCMA therapy before the 
index date for the purposes of subgroup analyses.
Study outcomes
Consistency between outcome definitions across data sources is another key consideration to 
minimize bias. Comparative effectiveness endpoints will be evaluated based on availability 
within each RWD source. Definitions of the outcomes will be aligned, where possible, with 
Study C1071003 (Table 2). In Study C1071003, the capture of objective response (OR) is 
defined according to IMWG criteria.

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Table 2. Definitions of comparative effectiveness outcomes in Study C1071003, Flatiron 
Health, and COTA
Outcome
Study C1071003
Flatiron Health
COTA
1
Objective 
response rate
(ORR)
The proportion of patients
with an OR based on 
blinded independent central 
review per IMWG criteria. 
OR is defined as having a 
best overall response of 
confirmed Stringent 
Complete Response (sCR), 
CR, Very Good Partial 
Response (VGPR), and PR 
per IMWG criteria, from the 
date of the first dose until 
confirmed PD, death or start 
of new anticancer therapy,
whichever occurs first.
The proportion of patients 
who achieved at least VGPR 
or PR 
Based on IMWG criteria*
The proportion of patients 
who achieved sCR, CR, 
VGPR, or PR
Based on IMWG criteria*
2
TTR
For patients with an OR per 
IMWG criteria, the time 
from the first dose to first 
documentation of OR that is 
subsequently confirmed.
For subjects with an OR
(based on PR or VGPR), time 
from the initiation of the first 
line after TCR to the first 
documented OR (first date at 
which at least VGPR or PR 
was documented).
For subjects with an OR, time 
from the initiation of the first 
line after TCR to the first 
documented OR.
3
Duration of 
response 
(DOR)
For patients with an OR per 
IMWG criteria, the time 
from the first 
documentation of OR that is 
subsequently confirmed, 
until confirmed PD per 
IMWG criteria, or death due 
to any cause, whichever 
occurs first.
Among patients who achieved 
an OR (based on PR or 
VGPR), the time from the first 
documentation of OR until 
progression or death due to 
any cause, whichever occurs 
first.
Among patients who achieved 
an OR, the time from the first 
documentation of OR until 
progression or death due to 
any cause, whichever occurs 
first.
Note:
*Details on the operational definitions of IMWG criteria used in Flatiron and COTA to define response, and 
a side-by-side comparison with the criteria used in Study C1071003 are provided in the relating study 
protocols as Document 001 and 002 in ANNEX 1. LIST OF STAND ALONE DOCUMENTS.
Other variables
Ensuring that baseline factors related to treatment assignment and outcomes are captured is 
of utmost importance for the validity of external control arms. The availability of these 
variables in selected RWD sources determines the feasibility of the external control arm.
Baseline covariates will be selected to compare patients from elranatamab and external 
control arms, and to perform further statistical adjustments to control for the baseline 
confounding (eg, via IPTW).

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Baseline covariates to be captured will include those related to patient demographic 
characteristics, disease characteristics, comorbidity profile, laboratory measurements, and 
MM treatment patterns, including LOT. The exact variables and definitions will be 
dependent upon availability within each RWD source. Adaptations of variable definitions or 
the use of proxy variables may be necessary if the preferred variables are unavailable in each 
data source. Each variable will be taken on or before the index date; if before, the most recent 
measurement will be used. All variables listed below will be used to describe the study 
cohorts and empirically reviewed for data completeness. Since small sample sizes may limit 
the number of covariates that can be reasonably accounted for in the statistical adjustment 
(eg, IPTW), a systematic literature review was conducted to identify the variables most 
strongly and consistently correlated with outcomes in RWD studies conducted among 
RRMM patients.  These variables would be prioritized for inclusion in the present study. 
Fifty-seven studies were extracted as part of our literature review which used either 
univariate (N=22) or multivariate (N=35) analyses to predict outcomes.  Collectively, these 
studies indicated the variables with the strongest relationships with future outcomes in an 
RRMM population were age, sex, cytogenetic risk, number of prior lines of therapy, and 
ISS/R-ISS.  Additionally, both hemoglobulin and albumin levels exhibited limited evidence 
as prognostic variables.
Priority covariates

Age at index date

Sex (male; female) 

ISS (International Staging System) stage (I; II; III) within 90 days before or on the 
index date, if feasible

ECOG performance status within 90 days before or on the index date, if feasible 

Time since initial MM diagnosis (years)

Number of pre-index treatment lines

Quad-and Penta-refractory status at index date

Cytogenic risk (high; standard) at index date, if feasible
Note that a high proportion of missingness is possible when using RWD and this may limit 
the feasibility to use the above variables (especially ISS and cytogenetic risk) as priority 
covariates in the statistical analysis.

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Additional covariates
Additional covariates will be collected to characterize patients from two study arms and to 
assess for baseline confounding adjustment. Given the adequate sample size, some of these 
covariates may be included in the analyses:

Race/ethnicity (White / Non-White)

Body mass index (kg/m2; identified from the most recent measure on or before the 
index date) 

Treatment setting (community-based; academic-based) at the index date

Extramedullary disease identified within 12 months before or on the index date

Presence of bone lesions within 12 months before or on the index date

Duration of prior therapy (days)

Stem cell transplantation (yes; no) within 12 months before or on the index date

Radiation therapy (yes; no) within 12 months before or on the index date

BCMA exposure during the baseline period 

History of any grade peripheral sensory or motor neuropathy for those with prior 
BCMA directed therapy

Charlson Comorbidity Index within 12 months before or on the index date 

Impaired cardiovascular function within 12 months before or on the index date

Basal cell or squamous cell skin cancer, or carcinoma in situ (yes; no) within 12 
months on or before the index date

Adequate hepatic function reported within 90 days before or on the index date

Adequate renal function reported within 90 days before or on the index date

Adequate BM function reported within 90 days before or on the index date

Aspartate aminotransferase (U/L) within 90 days before or on the index date, if 
feasible

Alanine aminotransferase (U/L) within 90 days before or on the index date, if feasible

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
Creatinine clearance (mL/min) within 90 days before or on the index date, if feasible

ANC (×109/L) within 90 days before or on the index date, if feasible

Platelets (×109/L) within 90 days before or on the index date, if feasible

Hemoglobin (g/L) within 90 days before or on the index date, if feasible

Calcium in serum or plasma (mg/dL) reported within 90 days before or on the index 
date

Lactate dehydrogenase (U/L) reported within 90 days before or on the index date

Beta-2 microglobulin (mg/L) reported within 90 days before or on the index date

Serum albumin (g/dL) reported within 90 days before or on the index date
9.4. Data sources
Data integration
Upon constructing the analytical file for the comparison between Study C1071003 and
Flatiron Health and between Study C1071003 and COTA, a common data model with
standardized data elements will be created and documented for transparency. The variable 
transformation will include the creation of the common variable type, format, and taxonomy. 
Consistent definitions will be applied to create derived variables for treatments, index date, 
outcomes, and comorbidities.
Combined study datasets
Combined study datasets will be created from the entirety of the Study C1071003 arm plus 
the selected external control arm based on data source and eligibility criteria.
A total of 4 combined study datasets will be created. Each will use the same patients from 
Study C1071003 along varying RW patients, depending upon the RWD source and 
inclusion/exclusion criteria applied to identify them, as indicated below.
For primary analyses:
Study C1071003 arm plus the external control arm selected using critical eligibility 
criteria from Flatiron Health.
Study C1071003 arm plus the external control arm selected using critical eligibility 
criteria from COTA.
For sensitivity analyses:
Study C1071003 arm plus the external control arm selected using expanded eligibility 
criteria from Flatiron Health.

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Study C1071003 arm plus the external control arm selected using expanded eligibility 
criteria from COTA.
9.5. Study size
The study sample will be identified from the analysis of secondary data that have already 
been collected. Accordingly, the sample size will be limited by the duration of the 
observation window. All patients who meet the inclusion/exclusion criteria defined in
Section 9.2.3 will be included in the analyses. Preliminary analysis of the Flatiron and COTA 
data identified 341 and 448 TCR MM patients before applying inclusions and exclusion 
criteria, respectively. No formal sample size estimations have been performed for this 
observational study.
9.6. Data management
This study will use structured databases from Study C1071003, an open-label, multi-center, 
non-randomized Phase 2 study of elranatamab (PF-06863135) monotherapy (Pfizer, 2021), 
Flatiron Health, and COTA (the latter two databases collect information on MM patients 
treated across the US). Flatiron and COTA have been selected according to data availability
and as fit-for-purpose for fulfilling study objectives (the US FDA, 2018 Framework). The 
dates for the study periods for each RW database have been selected to align as closely as 
possible to each other and to Study C1071003 which will include at least 9 months of follow-
up.
9.7. Data analyses
The detailed methods associated with the statistical analyses of the data collected in this 
study will be documented in the statistical analysis plan (SAP), which will be dated, filed, 
and maintained by the sponsor. Table 3 provides the summary of statistical analyses for the 
combined study cohorts.
Table 3. Summary of statistical analyses for combined study cohorts.
Analyses based on the 
critical eligibility criteria RW sample
Analyses based on the 
expanded eligibility criteria RW 
sample
Primary
analyses

Descriptive statistics of elranatamab and 
SOC-treated patients
Primary objective

Naïve (unadjusted) comparison of ORR
in elranatamab versus SOC-treated 
patients

IPTW comparison of ORR in 
elranatamab versus SOC-treated patients
Secondary objectives

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Table 3. Summary of statistical analyses for combined study cohorts.
Analyses based on the 
critical eligibility criteria RW sample
Analyses based on the 
expanded eligibility criteria RW 
sample

Naïve (unadjusted) comparison of TTR,
and DOR in elranatamab versus SOC-
treated patients

IPTW comparison of TTR, and DOR in 
elranatamab versus SOC-treated patients
Sensitivity 
analyses

Doubly robust comparisons of ORR in 
elranatamab versus SOC-treated patients

Quantitative bias assessments (using raw, 
IPTW, doubly robust estimates) when 
comparing ORR, TTR, and DOR in 
elranatamab versus SOC-treated patients

Descriptive statistics of 
elranatamab and SOC-treated 
patients

Naïve (unadjusted) comparison of 
ORR, TTR, and DOR in 
elranatamab versus SOC-treated 
patients

IPTW comparison of ORR, TTR,
and DOR in elranatamab versus 
SOC-treated patients

Doubly robust comparisons of 
ORR in elranatamab versus 
SOC-treated patients
Subgroup 
analyses
(if feasible)

Descriptive statistics of elranatamab and 
SOC-treated patients stratified by prior 
BCMA exposure

Naïve (unadjusted), IPTW, and doubly
robust comparisons of ORR in
elranatamab versus SOC-treated patients 
with and without prior BCMA exposure

Naïve (unadjusted) and IPTW
comparisons of TTR, and DOR in
elranatamab versus 
SOC-treated patients with and without 
prior BCMA exposure
In this study, measures taken to reduce potential bias include a pre-specified and detailed 
SAP. Additionally, the propensity score (PS) balancing steps will be conducted 
independently and prior to availability/knowledge of the outcomes (i.e., balancing will be 
conducted using only baseline characteristic data from an earlier data cut than the data cut 
which will contain the efficacy outcomes from Study C1071003).
9.7.1. Descriptive statistics
Tabular summaries of baseline patient demographics and clinical characteristics by treatment
arm will be presented. Summary statistics will include frequencies and percentages 
(categorical variables) and mean/median, minimum/maximum with standard 
deviation/interquartile range (continuous variables).

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9.7.2. Primary analyses
For comparative effectiveness, ORR, TTR, and DOR will be assessed using IPTW
comparisons estimating the average treatment effect (ATE). The naïve (unadjusted) estimates 
for ORR, TTR and DOR will be reported.
Propensity scores and inverse probability of treatment weighting
In analyses of RWD, an important consideration in the identification of potentially causal 
effects is the control for confounding. IPTW is a well-established method for causal 
inference in nonrandomized studies. Estimating the PS is a form of dimensionality reduction, 
in which several individual characteristics relevant to treatment assignment and the outcome, 
or those related only to outcome development, are used to estimate the conditional 
probability that the patient is assigned to a given treatment. IPTW is a quasi-experimental 
approach used to create a pseudo-population in which the covariates are independent of the 
treatment assignment, thereby permitting an unbiased estimate of the ATE.
The PS will be estimated using logistic regression models, where the dependent variable is a 
binary indicator of the treatment arm (elranatamab versus SOC). Covariates in the logistic 
regression will include the priority covariates described in Section 9.3 and, optional, some 
additional covariates. Diagnostics of the estimated PS will be applied by examining the 
distribution of the PS in each treatment group, the area of PS overlap, or any outliers. The 
estimated PS will be used to generate stabilized IPTWs. A standardized mean difference
(SMD) of ≥10% will be used to identify potential residual confounding and as an indicator of 
covariate imbalance between the treatment arms requiring further investigation(Austin, 
2009). Grossly higher SMDs (over 25%) may lead to refining the logistic model for deriving 
the weights.
Analysis models for endpoints
The following analyses will be performed for endpoints.
Objective response
The dichotomous outcome ORR will be compared between treatment arms using a logistic 
regression model. Unweighted and IPTW estimates will be reported together with 
corresponding 95% CIs. Standard errors and CIs for the IPTW estimators will be obtained 
via a robust sandwich-type estimator of variance (Lin and Wei, 1989).
Time to event endpoints (TTR and DOR)
TTR and DOR will be compared between treatment arms using hazard ratios estimated from 
Cox proportional hazards models. The proportional hazards assumption will be checked, and 
in case of deviations, a restricted mean survival time model will be applied instead of the 
Cox proportional hazards regression model (Zhao and Tsiatis, 1999) Standard errors and CI
for the IPTW estimator will be obtained via a robust sandwich-type estimator of variance 
(Lin and Wei, 1989).
Kaplan-Meier figures will be used for DOR to visually examine survival probabilities over 
the follow-up period. Results from both weighted and unweighted analyses will be provided.

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9.7.3. Sensitivity analyses
To evaluate the robustness of results from the primary analyses, sensitivity analyses will be 
conducted.
Doubly robust comparison
The dichotomous outcome ORR will be compared between treatment arms using doubly 
robust methods. Analyses employing a doubly robust estimator require fitting 2 models: a 
model for treatment or exposure status, and a second model for the outcome of interest. As 
with other causal inference methods, valid and unbiased estimates require assumptions of no 
unmeasured confounding (exchangeability), positivity (the experimental treatment 
assumption), no interference, and consistency (Funk et al., 2011). Assuming these 
assumptions are upheld, if at least 1 of these 2 models is correctly specified, resulting in a 
doubly robust estimate that may remain consistent and unbiased (Bang and Robins, 2005).
The AIPW approach will be used to estimate a PS model for weighting, and subsequently 
augment the inverse probability weights using predicted values from the outcome model. The 
general procedure for estimation of PS, and IPTW is provided in Section 9.7.2.
Diagnostics will be applied to assess whether the doubly robust model appears to be 
well-specified (Austin and Stuart, 2015).
Alternative eligibility criteria
To assess the potential influence of population selection on the observed effect estimates, 
additional analysis will be performed identical to the primary analysis but using the 
combined study cohorts with the expanded eligibility criteria.
Subgroup analysis by prior BCMA exposure
A subgroup analysis by prior BCMA therapy (yes/no) was intended to be performed if at 
least 
20 patients with prior BCMA exposure were available in at least one of the external
comparator arms. However, based on preliminary assessment of the Flatiron and COTA data, 
the minimum sample size of BCMA-exposed patients is not met in either comparator arm; 
therefore, only a subgroup analysis of non-BCMA-exposed patients will be performed. This
analysis will only be performed for the primary analysis and not for sensitivity analyses 
unless stated otherwise.
Nullification analysis
Nullification analysis will be applied to assess the potential influence of unmeasured 
confounding on the observed associations. A shortlist of suspected unmeasured confounders 
will be identified; these are variables that were observed in Study C1071003 but not available 
(or only with substantial missingness) in the RWD sources. The E-value will be computed 
and reflects the minimum strength of association the confounder would need to have with the 
exposure and outcome, conditional on the measured covariates, to fully explain away the 
observed treatment effect (van der Weele and Ding, 2017). This sensitivity analysis will be 
applied for the primary analysis.

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E-values are relatively intuitive, and offer a comprehensible, easily communicated summary 
of the findings. The lowest possible E-value is 1, and as the value increases, so does the 
implied degree of bias required to explain the results (van der Weele and Ding, 2017).
E-values will be computed for measures of effect and adjusted for the same set of relevant 
covariates as in the primary analyses.
9.8. Quality control
This is a retrospective study, so issues of quality control at study sites, e.g., data queries, do 
not apply. Analyses are programmed according to the specifications in the protocol, and if 
applicable, the statistical analysis plan and documented in a programming plan. Final
deliverables are reviewed and verified by a second, independent programmer who may also 
perform double programming. All quality checks are documented in the programming plan.
9.9. Limitations of the research methods
Unlike clinical trial settings with specific definitions of study outcomes and scheduled 
assessments described in the protocol, the assessment of TTR in RW clinical practice settings 
may not be made consistently across patients and physicians. Specifically, in real-world 
observational studies, especially those performed retrospectively, it is not possible to 
implement consistent monitoring and application of homogenous evaluation criteria (eg, 
IMWG) that are inherent to clinical trial design. As such, depending on how often clinical 
assessments are made, outcomes may be subject to surveillance bias, which occurs when the 
outcome is more likely to be captured among patients who are followed more closely (Haut 
and Pronovost, 2011). This bias could favor the RW control groups, considering that in real 
life, the patient is monitored less frequently for progression.
The use of 2 RWD sources has further limitations. First, missing data and the accuracy of 
recorded data on disease characteristics, lab results, and comorbidities in RWD may 
introduce an information bias and residual confounding. Second, patients without sufficient 
information in their EHRs were excluded from the datasets by the data providers to avoid 
information bias. However, this may introduce a selection bias. Third, the variability in 
populations and differences in a and/or variables/covariates can result in changes in 
evaluations.
To address and/or reduce the impact of potential bias and improve exchangeability between 
the trial and the external control arms (Pocock, 1976; Ghadessi et al., 2020; Hatswell et al., 
2020) measures will be taken to align comparable populations, advanced adjustment methods 
will be employed, and a series of sensitivity analyses will be conducted to evaluate the 
impact of key assumptions and selection criteria. However, this analysis is still subject to 
unmeasured confounding. Quantitative bias analysis will attempt to estimate the potential 
bias from unmeasured confounders, but these estimates are likely to be conservative and may 
nullify a true treatment effect.
9.10. Other aspects
Not applicable.

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10. PROTECTION OF HUMAN SUBJECTS
10.1. Patient information
This study involves data that exist in anonymized structured format and contain no patient 
personal information.
10.2. Patient consent
As this study involves anonymized structured data, which according to applicable legal 
requirements do not contain data subject to privacy laws, obtaining informed consent from 
patients by Pfizer is not required.
10.3. Patient withdrawal
Not applicable
10.4. Institutional review board (IRB)/ Independent ethics committee (IEC)
Approval from an institutional review board/independent ethics committee is not required for 
this study as only de-identified secondary data sources and anonymized medical record data 
from EHR will be used. Therefore, this study is considered exempt from the requirements for 
“human subjects research”.
10.5. Ethical conduct of the study
The study will be conducted in accordance with legal and regulatory requirements, as well as 
with scientific purpose, value, and rigor and follow generally accepted research practices 
described in Guidelines of Good Pharmacoepidemiology Practices (GPP) issued by the 
International Society for Pharmacoepidemiology (ISPE), Good Practices for Outcomes 
Research issued by the International Society for Pharmacoeconomics and Outcomes 
Research (ISPOR), International Ethical Guidelines for Epidemiological issued by the 
Council for International Organizations of Medical Sciences (CIOMS).
11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS
This study is retrospective in nature, it involves data that exist as structured data by the time 
of study start or a combination of existing structured data and unstructured data, which will 
be converted to structured form during the implementation of the protocol solely by a 
computer using automated/algorithmic methods, such as natural language processing.
In these data sources, individual patient data are not retrieved or validated, and it is not 
possible to link (ie, identify a potential association between) a particular product and medical 
event for any individual. Thus, the minimum criteria for reporting an AE (ie, identifiable 
patient, identifiable reporter, a suspect product, and event) cannot be met.
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
For all publications relating to the study, Pfizer will comply with recognized ethical
standards concerning publications and authorship, including Section II - “Ethical

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Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
In the event of any prohibition or restriction imposed (e.g., clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator party responsible for 
collecting data from the participant is aware of any new information which might influence 
the evaluation of the benefits and risks of a Pfizer product, Pfizer should be informed 
immediately.
13. REFERENCES
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Austin, P.C. and Stuart, E.A. (2015) ‘Moving towards best practice when using inverse 
probability of treatment weighting (IPTW) using the propensity score to estimate causal 
treatment effects in observational studies’, Statistics in Medicine, 34(28), pp. 3661–3679. 
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Bang, H. and Robins, J.M. (2005) ‘Doubly Robust Estimation in Missing Data and Causal 
Inference Models’, Biometrics, 61(4), pp. 962–973. Available at: 
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Carroll, NM. (2016) ‘Application of Propensity Score Models in Observational Studies using 
VDW data’, pp. 2522–2018.
Chesnaye, N.C. et al. (2022) ‘An introduction to inverse probability of treatment weighting 
in observational research’, Clinical Kidney Journal, 15(1), pp. 14–20. Available at: 
https://doi.org/10.1093/CKJ/SFAB158.
COTA. Multiple myeloma real-world evidence. Data manual. (2022).
Committee for Medicinal Products for Human Use (CHMP) guideline on clinical trials in 
small populations draft agreed by efficacy working party/ad hoc group on clinical trials in 
small populations adoption by CHMP for release for consultation. (2002). Available at: 
http://www.emea.eu.int (Accessed: 24 April 2022).
Flatiron Health, Inc. (2021) Analytic guide for Flatiron Health Data. Triple-class refractory 
multiple myeloma. Version 1.
‘Framework for FDA’s Real-World Evidence Program’ (2018). Available at: www.fda.gov 
(Accessed: 24 May 2022).
Funk, M.J. et al. (2011) ‘Doubly Robust Estimation of Causal Effects’, American Journal of 
Epidemiology, 173(7), pp. 761–767. Available at: https://doi.org/10.1093/aje/kwq439.
Gandhi, U.H. et al. (2019) ‘Outcomes of patients with multiple myeloma refractory to CD38-
targeted monoclonal antibody therapy’, Leukemia, 33(9), pp. 2266–2275. Available at: 
https://doi.org/10.1038/S41375-019-0435-7.
Ghadessi, M. et al. (2020) ‘A roadmap to using historical controls in clinical trials - By Drug 
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Orphanet Journal of Rare Diseases, 15(1). Available at: https://doi.org/10.1186/S13023-020-
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Hatswell, A. et al. (2020) ‘Summarising salient information on historical controls: A 
structured assessment of validity and comparability across studies’, Clinical Trials, 17(6), pp. 
607–616. Available at: https://doi.org/10.1177/1740774520944855.
Haut, E.R. and Pronovost, P.J. (2011) ‘Surveillance bias in outcomes reporting’, JAMA -
Journal of the American Medical Association, 305(23), pp. 2462–2463. Available at: 
https://doi.org/10.1001/JAMA.2011.822.
ICH E10 Choice of control group in clinical trials | European Medicines Agency (2001). 
Available at: https://www.ema.europa.eu/en/ich-e10-choice-control-group-clinical-trials 
(Accessed: 24 May 2022).
Jagannath, S. et al. (2020) ‘KarMMa-RW: A study of real-world treatment patterns in 
heavily pretreated patients with relapsed and refractory multiple myeloma (RRMM) and 
comparison of outcomes to KarMMa.’, Journal of Clinical Oncology, 38(15_suppl), pp. 
8525–8525. Available at: https://doi.org/10.1200/JCO.2020.38.15_SUPPL.8525.
Jahanshahi, M. et al. (2021) ‘The Use of External Controls in FDA Regulatory Decision 
Making’, Therapeutic innovation & regulatory science, 55(5), pp. 1019–1035. Available at: 
https://doi.org/10.1007/S43441-021-00302-Y.
Lin, D.Y. and Wei, L.J. (1989) ‘The Robust Inference for the Cox Proportional Hazards 
Model’, Journal of the American Statistical Association, 84(408), p. 1074. Available at: 
https://doi.org/10.2307/2290085.
Mikhael, J. (2020) ‘Treatment Options for Triple-class Refractory Multiple Myeloma’, 
Clinical lymphoma, myeloma & leukemia, 20(1), pp. 1–7. Available at: 
https://doi.org/10.1016/J.CLML.2019.09.621.
Nooka, A.K. et al. (2015) ‘Treatment options for relapsed and refractory multiple myeloma’, 
Blood, 125(20), pp. 3085–3099. Available at: https://doi.org/10.1182/BLOOD-2014-11-
568923.
Padala, S.A. et al. (2021) ‘Epidemiology, Staging, and Management of Multiple Myeloma’, 
Medical sciences (Basel, Switzerland), 9(1), p. 3. Available at: 
https://doi.org/10.3390/MEDSCI9010003.
Pfizer (2021) MagnetisMM-3, an open-label, multicenter, non-randomized phase 2 study of 
elranatamab (pf-06863135) monotherapy in participants with MM who are refractory to at 
least one proteasome inhibitor (PI), one immunomodulatory drug, and one anti-CD38 
antibody. Final Protocol Amendment 7, 11 November 2021.
Pfizer Initiates Pivotal Phase 2 MagnetisMM-3 Trial of BCMA-CD3 Bispecific Antibody 
Elranatamab (PF-06863135) in Multiple Myeloma | Pfizer (2022). Available at: 
https://www.pfizer.com/news/press-release/press-release-detail/pfizer-initiates-pivotal-phase-
2-magnetismm-3-trial-bcma (Accessed: 24 May 2022).
Pfizer Presents First Data from Planned Interim Analysis of Pivotal Phase 2 MagnetisMM-3 
Trial of BCMA-CD3 Bispecific Antibody Elranatamab Under Investigation for 
Relapsed/Refractory Multiple Myeloma | Pfizer (2022). Available at: 
https://www.pfizer.com/news/press-release/press-release-detail/pfizer-presents-first-data-
planned-interim-analysis-pivotal (Accessed: 26 June 2022).
Pocock, S.J. (1976) ‘The combination of randomized and historical controls in clinical trials’, 
Journal of chronic diseases, 29(3), pp. 175–188. Available at: https://doi.org/10.1016/0021-
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Rajkumar, S.V. et al. (2014) ‘International Myeloma Working Group updated criteria for the 
diagnosis of multiple myeloma’, The Lancet. Oncology, 15(12), pp. e538–e548. Available at: 
https://doi.org/10.1016/S1470-2045(14)70442-5.
Rare Diseases: Natural History Studies for Drug Development | FDA (2019). Available at: 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/rare-diseases-
natural-history-studies-drug-development (Accessed: 24 May 2022).
Sebag, M. et al. (2022) ‘Elranatamab (PF-06863135), a B-Cell Maturation Antigen (BCMA) 
Targeted CD3-Engaging Bispecific Molecule, for Patients with Relapsed or Refractory 
Multiple Myeloma: Results from Magnetismm-1’. Available at: 
https://ash.confex.com/ash/2021/webprogram/Paper150519.html (Accessed: 24 April 2022).
Wallington-Beddoe, C.T. and Pitson, S.M. (2017) ‘Novel therapies for multiple myeloma’, 
Aging, 9(8), pp. 1857–1858. Available at: https://doi.org/10.18632/AGING.101284.
van der Weele, T.J. and Ding, P. (2017) ‘Sensitivity Analysis in Observational Research: 
Introducing the E-Value’, Annals of internal medicine, 167(4), pp. 268–274. Available at: 
https://doi.org/10.7326/M16-2607.
Yong, K. et al. (2016) ‘Multiple myeloma: patient outcomes in real-world practice’, British 
journal of haematology, 175(2), pp. 252–264. Available at: 
https://doi.org/10.1111/BJH.14213.
Zhao, H. and Tsiatis, A.A. (1999) ‘Efficient estimation of the distribution of quality-adjusted 
survival time’, Biometrics, 55(4), pp. 1101–1107. Available at: 
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14. LIST OF TABLES
Table 1. Inclusion and Exclusion criteria for Study C1071003, Flatiron Health, and 
COTA .......................................................................................................18
Table 2. Definitions of comparative effectiveness outcomes in Study C1071003, 
Flatiron Health, and COTA ......................................................................21
Table 3. Summary of statistical analyses for combined study cohorts....................................25

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15. LIST OF FIGURES
Figure 1. Baseline and observation periods in Study C1071003.............................................15
Figure 2. Baseline and observation periods in external control arms......................................15

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16. APPENDIX
16.1. Appendix. Inclusion and exclusion criteria in Study C1071003, Flatiron Health and COTA.
Patient inclusion criteria per 
C1071003 Study  
Flatiron Spotlight RW alternative 
approach to be used in the external 
control arm
Implementation
COTA RW alternative 
approach to be used in the 
external control arm
Implementation
Age and Sex:
Male or female participants age ≥18 
years.
Male or female participants age ≥18 
years.
Critical and 
expanded 
criteria
Male or female participants age 
≥18 years.
Critical and 
expanded 
criteria
A female participant is eligible to 
participate if she is not pregnant or 
breastfeeding. 
Not available.
N/A
Not available.
N/A
Type of Participant and Disease Characteristics:
Participants who are willing and able 
to comply with all scheduled visits, 
treatment plan, laboratory tests, 
lifestyle considerations, and other 
study procedures.
Not applicable
N/A
Not applicable
N/A
Prior diagnosis of MM as defined 
according to IMWG criteria 
(Rajkumar et al, 2014). 
Perfect or close match
Patients were extracted by Flatiron based 
on the presence of a diagnosis code for 
MM (ICD-9 203.0x or ICD-10 C90.0x) 
any time prior to the index date. Active 
MM diagnosis was confirmed by 
Flatiron via abstraction of unstructured 
data. 
Critical and 
expanded 
criteria
Perfect or close match
MM diagnosis confirmed 
through pathology reports or 
through clinical diagnosis and 
supporting documentation such 
as lab tests.
Critical and 
expanded 
criteria

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Patient inclusion criteria per 
C1071003 Study  
Flatiron Spotlight RW alternative 
approach to be used in the external 
control arm
Implementation
COTA RW alternative 
approach to be used in the 
external control arm
Implementation
Measurable disease based on IMWG 
criteria as defined by at least 1 of the 
following:
a. Serum M-protein ≥0.5 g/dL by 
SPEP
b. Urinary M-protein excretion ≥200 
mg/24 hours by UPEP
c. Serum immunoglobulin FLC ≥10 
mg/dL (≥100 mg/L) AND abnormal 
serum immunoglobulin kappa to 
lambda FLC ratio (<0.26 or >1.65)
Perfect or close match.
Measurable disease, defined within 90 
days prior to or on the index date.
Critical and 
expanded 
criteria
Perfect or close match.
Measurable disease, defined 
within 90 days before or on the 
index date.
Critical and 
expanded 
criteria
Refractory to at least one IMiD.
Perfect or close match. 
Refractory to at least one IMiD defined 
as disease progression, based on IMWG 
criteria or HCP assessment, while a 
patient is on therapy or within 60 days of 
the last therapy dose in any line, 
regardless of response. 
Critical and 
expanded 
criteria
Perfect or close match. 
Refractory to at least one IMiD 
defined as disease progression, 
based on IMWG criteria or HCP 
assessment, while a patient is on 
therapy or within 60 days of the 
last therapy dose in any line, 
regardless of response.
Critical and 
expanded 
criteria
Refractory to at least one PI.
Perfect or close match. 
Refractory to at least one PI defined as 
disease progression, based on IMWG 
criteria or HCP assessment, while a 
patient is on therapy or within 60 days of 
the last therapy dose in any line,
regardless of response.
Critical and 
expanded 
criteria
Perfect or close match. 
Refractory to at least one PI 
defined as disease progression, 
based on IMWG criteria or HCP 
assessment, while a patient is on 
therapy or within 60 days of the 
last therapy dose in any line, 
regardless of response. 
Critical and 
expanded 
criteria

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Patient inclusion criteria per 
C1071003 Study  
Flatiron Spotlight RW alternative 
approach to be used in the external 
control arm
Implementation
COTA RW alternative 
approach to be used in the 
external control arm
Implementation
Refractory to at least one anti-CD38 
antibody.
Perfect or close match. 
Refractory to at least one anti-CD38 
defined as disease progression, based on 
IMWG criteria or HCP assessment, 
while a patient is on therapy or within 60 
days of the last therapy dose in any line, 
regardless of response. 
Critical and 
expanded 
criteria
Perfect or close match. 
Refractory to at least one anti-
CD38 defined as disease 
progression, based on IMWG 
criteria or HCP assessment, 
while a patient is on therapy or 
within 60 days of the last 
therapy dose in any line, 
regardless of response. 
Critical and 
expanded 
criteria
Relapsed/refractory to last anti-MM 
regimen.
Note: Refractory is defined as having 
progressive disease while on therapy 
or within 60 days of the last dose in 
any line, regardless of response.
Perfect or close match
By design as the index date is the first 
line after the TCR eligibility date, all 
patients will be refractory to the last anti-
myeloma regimen.
Critical and 
expanded 
criteria
Perfect or close match
By design as the index date is 
the first line after the TCR 
eligibility date, all patients will 
be refractory to the last anti-
myeloma regimen.
Critical and 
expanded 
criteria
Cohort A: Has not received prior 
BCMA-directed therapy.
Information is collected as baseline 
covariates.
Possible 
inclusion 
criteria for 
subgroup 
analysis
Information is collected as 
baseline covariates.
Possible 
inclusion 
criteria for 
subgroup 
analysis
Cohort B: Has received prior BCMA-
directed ADC or BCMA-directed 
CAR T-cell therapy, either approved 
or investigational.
Information is collected as baseline 
covariates.
Possible 
inclusion 
criteria for 
subgroup 
analysis
Information is collected as 
baseline covariates.
Possible 
inclusion 
criteria for 
subgroup 
analysis

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Patient inclusion criteria per 
C1071003 Study  
Flatiron Spotlight RW alternative 
approach to be used in the external 
control arm
Implementation
COTA RW alternative 
approach to be used in the 
external control arm
Implementation
ECOG performance status ≤2. 
Perfect or close match. 
ECOG performance status ≤2 within 90 
days prior to or on the index date
Critical and 
expanded 
criteria
Perfect or close match. 
ECOG performance status ≤2 
within 90 days prior to or on the 
index date
KPS score to be converted to 
ECOG if patient's performance 
status test closest to the index 
date is KPS
Critical and 
expanded 
criteria
LVEF ≥40% as determined by a 
MUGA scan or ECHO.
Not available. 
N/A
Not available. 
N/A
Adequate hepatic function 
characterized by the following:
a. Total bilirubin ≤2 x ULN (≤3 x 
ULN if documented Gilbert’s 
syndrome);
b. AST ≤2.5 x ULN; and
c. ALT ≤2.5 x ULN
Perfect or close match
Adequate hepatic function within 30 
days before study index date.
Baseline 
covariate, 
expanded 
criteria
Perfect or close match
Adequate hepatic function 
within 30 days before study 
index date.
Baseline 
covariate, 
expanded 
criteria
Adequate renal function defined by 
an estimated creatinine clearance ≥30 
mL/min (according to the Cockcroft 
Gault formula, by 24-hours urine 
collection for creatinine clearance, or 
according to local institutional 
standard method).
Perfect or close match
Adequate renal function within 30 days 
before study index date.
Baseline 
covariate, 
expanded 
criteria
Perfect or close match
Adequate renal function within 
30 days before study index date.
Baseline 
covariate, 
expanded 
criteria

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Patient inclusion criteria per 
C1071003 Study  
Flatiron Spotlight RW alternative 
approach to be used in the external 
control arm
Implementation
COTA RW alternative 
approach to be used in the 
external control arm
Implementation
Adequate BM function characterized 
by the following:
a. ANC ≥1.0 × 109
/L (use of granulocyte-colony 
stimulating factors is permitted if 
completed at least 7 days prior to 
planned start of dosing);
b. Platelets ≥25 × 109
/L (transfusion support is permitted if 
completed at least 
7 days prior to planned start of 
dosing); and
c. Hemoglobin ≥8 g/dL (transfusion 
support is permitted if completed at 
least 
7 days prior to planned start of 
dosing).
Perfect or close match
Adequate BM function within 90 days 
before study index date.
Baseline 
covariate, 
expanded 
criteria
Perfect or close match
Adequate BM function within 
90 days before study index date.
Baseline 
covariate, 
expanded 
criteria
Resolved acute effects of any prior 
therapy to baseline severity or 
CTCAE Grade ≤1.
Not available.
N/A
Not available. 
N/A
Informed Consent:
Capable of giving signed informed 
consent, which includes compliance 
with the requirements and restrictions 
listed in the ICD and in this protocol.
Not applicable
N/A
N/A
N/A

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Patient exclusion criteria per 
C1071003 Study  
Flatiron Spotlight RW alternative 
approach to be used in the external 
control arm
Implementation
COTA RW alternative approach to 
be used in the external control arm
Implementation
Medical Conditions:
Smoldering MM.
Not Available
Not identifiable directly in Flatiron 
Spotlight data however patients are only 
included in the data if they have 
evidence of active MM. Since 
smoldering MM (SMM) can be a 
precursor to active MM, patients may 
have had SMM before progressing to 
active MM.
Not implemented 
directly
Perfect or close match
Patient will be excluded if SMM is 
the type of MM listed for the patient 
closet to (but not after) the index date
Critical and 
expanded 
criteria
Active plasma cell leukemia.
Perfect or close match
Diagnosis of plasma cell leukemia is 
identified based on the presence of ≥1 
diagnosis code within the 365 days prior 
to or on the index date, or based on 
identification of plasma cell leukemia in 
enhanced data abstracted from 
unstructured sources.
Critical and 
expanded criteria
Perfect or close match
Active plasma cell leukemia within 
the 365 days before or on the index 
date can be identified in the secondary 
disease diagnosis dataset.
Patients are censored by COTA and 
no longer followed in the data after a 
determination of active plasma cell 
leukemia.
Critical and 
expanded 
criteria
Amyloidosis. 
Perfect or close match
Diagnosis of amyloidosis is identified 
based on the presence of ≥1 diagnosis 
code within the 365 days prior to or on 
the index date, or based on 
identification of amyloidosis in 
enhanced data abstracted from 
unstructured sources.
Critical and 
expanded criteria
Perfect or close match
Amyloidosis within the 365 days 
before or on the index date can be 
identified in the secondary disease 
diagnosis dataset.
Patients are censored by COTA and 
no longer followed in the data after a 
diagnosis of amyloidosis.
Critical and 
expanded 
criteria

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Patient exclusion criteria per 
C1071003 Study  
Flatiron Spotlight RW alternative 
approach to be used in the external 
control arm
Implementation
COTA RW alternative approach to 
be used in the external control arm
Implementation
POEMS syndrome
Not available
N/A
Not available
N/A
Stem cell transplant within 12 weeks 
prior to enrollment or active GVHD.
Perfect or close match
Diagnosis of GVHD is identified based 
on the presence of ≥1 diagnosis code 
within the 12 weeks prior to or on the 
index date, but there are no specific 
codes for “active”. 
The indicator of stem cell transplant and 
the date the patient received the stem 
cell transplant is provided. 
Critical and 
expanded criteria
Partial match.
Stem cell transplants within 12 weeks 
prior to index date.
Critical and 
expanded 
criteria
Impaired cardiovascular function or 
clinically significant cardiovascular 
diseases, defined as any of the 
following within 6 months prior to 
enrollment:
a. Acute myocardial infarction or 
acute coronary syndromes (eg, 
unstable angina, coronary artery 
bypass graft, coronary angioplasty 
or stenting, symptomatic pericardial 
effusion);
b. Clinically significant cardiac 
arrhythmias (eg, uncontrolled atrial 
fibrillation or uncontrolled 
paroxysmal supraventricular 
tachycardia);
Partial match
Identifiable based on diagnosis codes 
(except for QT syndrome); enhanced 
data abstracted from unstructured 
sources can identify the following CV 
conditions:  angina, 
atrial arrhythmia, cerebrovascular 
accident, 
congestive heart failure, 
DVT, MI, another arrhythmia, PE, TIA, 
ventricular arrhythmia.
However, for arrhythmias there is no 
information as to their clinically 
significance (eg, if the arrhythmia is 
uncontrolled).
Baseline covariate, 
expanded criteria
Partial match
Identifiable based on comorbid 
conditions that are included in the 
CCI.
However, comorbid conditions 
included in the CCI are only captured 
once per patient.
History of cardiac arrhythmia, QT 
syndrome, and other forms of acute 
coronary syndrome are not 
identifiable.
Baseline 
covariate, 
expanded 
criteria

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Patient exclusion criteria per 
C1071003 Study  
Flatiron Spotlight RW alternative 
approach to be used in the external 
control arm
Implementation
COTA RW alternative approach to 
be used in the external control arm
Implementation
c. Thromboembolic or 
cerebrovascular events (eg, transient 
ischemic attack, cerebrovascular 
accident, deep vein thrombosis 
[unless associated with a central 
venous access complication] or 
pulmonary embolism);
d. Prolonged QT syndrome (or 
triplicate average QTcF >470 msec 
at screening). 
Ongoing Grade ≥2 peripheral 
sensory or motor neuropathy. 
Partial match.
Ongoing Grade ≥2 peripheral sensory or 
motor neuropathy cannot be identified 
in the data as there is no information 
about Grade. 
However, treatments used to manage 
neuropathic pain will be used as a proxy 
to identify presence of more severe 
neuropathy cases to describe patients 
Baseline covariate, 
expanded criteria
Not available
N/A
History of any grade peripheral 
sensory or motor neuropathy with 
prior BCMA-directed therapy 
(Cohort B).
Perfect or close match
Sensory and motor neuropathy may be 
identified based on the presence of ≥1 
diagnosis code any time prior to or on 
the index date.
Among patients with prior BCMA-
directed therapy only.
Possible exclusion 
criteria for 
subgroup analysis
Perfect or close match
May be identified based on AEs that 
resulted in BCMA treatment 
discontinuation
Possible 
exclusion 
criteria for 
subgroup 
analysis

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Patient exclusion criteria per 
C1071003 Study  
Flatiron Spotlight RW alternative 
approach to be used in the external 
control arm
Implementation
COTA RW alternative approach to 
be used in the external control arm
Implementation
History of GBS or GBS variants, or 
history of any Grade ≥3 peripheral 
motor polyneuropathy.
Partial match
GBS could be identified based on 
diagnosis codes. There is no information 
about the grade in the data that allows 
us to identify Grade ≥3 peripheral motor 
polyneuropathy. Treatments used to 
manage neuropathic pain will be used as 
a proxy to identify more severe 
neuropathy cases. 
Baseline covariate, 
expanded criteria
Not available
N/A
Active HBV, HCV, SARS-CoV2, 
HIV, or any active, uncontrolled 
bacterial, fungal, or viral 
infection. Active infections must be 
resolved at least 14 days prior to 
enrollment. 
Partial match
Identifiable based on lab tests as well as 
diagnosis codes. There are no specific 
codes for “active” or “uncontrolled”, but 
“active” infections will be closely 
approximated using clinically plausible 
covariate assessment periods. HBV or 
HIV any time before index. Other 
infections within 30 days before index.
Critical and 
expanded criteria
Partial match
HBV, HCV, and HIV at any time 
before index (comorbidities including 
these infections are only captured 
once per patient).
No information for SARS-CoV2.
Information on infections is not 
available through lab data.
Critical and 
expanded 
criteria

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Patient exclusion criteria per 
C1071003 Study  
Flatiron Spotlight RW alternative 
approach to be used in the external 
control arm
Implementation
COTA RW alternative approach to 
be used in the external control arm
Implementation
Any other active malignancy within 
3 years prior to enrollment, except 
for adequately treated basal cell or 
squamous cell skin cancer, or
carcinoma in situ.
Perfect or close match.
Will be identified based on the presence 
of ≥1 diagnosis code of any other 
malignancy, except for adequately 
treated basal cell or squamous cell skin 
cancer, or carcinoma in situ within the 
3 years prior to or on the index date. 
"Adequately treated" is not identifiable 
therefore all basal or squamous cell skin 
cancer or carcinoma in situ will be 
considered adequately treated and not 
reason for exclusion.
Critical and 
expanded criteria
Perfect or close match.
Any secondary malignancy developed 
up to 3 years before index treatment. 
Only secondary malignancies 
diagnosed between initial MM 
diagnosis and index date are 
identifiable. COTA will censor 
patients who develop a secondary 
cancer after initial MM diagnosis.
Critical and 
expanded 
criteria
Other surgical (including major 
surgery within 14 days prior to 
enrollment), medical or psychiatric 
conditions including recent (within 
the past year) or active suicidal 
ideation/behavior or laboratory 
abnormality that may increase the 
risk of study participation or, in the 
investigator’s judgment, make the 
participant inappropriate for the 
study.
Not available
N/A
N/A
N/A
Prior/Concomitant Therapy:
Previous treatment with an 
anti-BCMA bispecific antibody.
Partial match
Only non-investigational agents are 
identifiable, therefore to ensure no 
exposure to anti-BCMA bispecific 
antibody treatment, all patients treated 
(Baseline covariate 
- investigational 
agents), expanded 
criteria
Partial match
Only non-investigational agents are 
identifiable, therefore to ensure no 
exposure to anti-BCMA bispecific 
antibody treatment, all patients treated 
(Baseline 
covariate as an 
investigational
agents), 
expanded 
criteria

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Patient exclusion criteria per 
C1071003 Study  
Flatiron Spotlight RW alternative 
approach to be used in the external 
control arm
Implementation
COTA RW alternative approach to 
be used in the external control arm
Implementation
with investigational agents would need 
to be excluded
with investigational agents would 
need to be excluded
Prior/Concurrent Clinical Study Experience:
Previous administration with an 
investigational drug within 30 days 
(or as determined by the local 
requirement) or 5 half-lives 
preceding the first dose of study 
intervention used in this study 
(whichever is longer). 
Perfect or close match.
Previous administration with an 
investigational drug within 30 days 
before the index date or on index date.
Critical and 
expanded criteria
Perfect or close match.
Previous administration with an 
investigational drug within 30 days 
before the index date or on index date.
Critical and 
expanded 
criteria

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Other Exclusions:
Investigator site staff or Pfizer 
employees directly involved in the 
conduct of the study, site staff 
otherwise supervised by the 
investigator, and their respective 
family members. 
Not applicable
N/A
N/A
N/A
Known or suspected hypersensitivity 
to the study intervention or any of its 
excipients.
Not applicable
N/A
N/A
N/A
Live attenuated vaccine must not be 
administered within 4 weeks of the 
first dose of study intervention. 
Not available. 
N/A
N/A
N/A

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17. ANNEX 1. LIST OF STAND ALONE DOCUMENTS
Number
Document 
Reference 
Number
Date
Title
001
001
11-Mar-2019
Protocol for Flatiron database (“Retrospective 
study of treatment patterns and clinical outcomes 
in patients with triple class refractory MM treated 
in a real-world setting”)
002
002
17-May-
2022
Protocol for COTA database (“Retrospective study 
of treatment patterns and clinical outcomes in 
patients with triple class refractory MM treated in 
a real-world setting”)