HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
COLUMVITM safely and effectively. See full prescribing information for
COLUMVI.
COLUMVI (glofitamab-gxbm) injection, for intravenous use
Initial U.S. Approval: 2023--------------------- DOSAGE FORMS AND STRENGTHS --------------------Injection:
 2.5 mg/2.5 mL (1 mg/mL) in a single-dose vial. (3) 10 mg/10 mL (1 mg/mL) in a single-dose vial. (3)------------------------------ CONTRAINDICATIONS ------------------------------WARNING: CYTOKINE RELEASE SYNDROME
See full prescribing information for complete boxed warning

None. (4)----------------------- WARNINGS AND PRECAUTIONS -----------------------

Cytokine Release Syndrome (CRS), including serious or fatal
reactions, can occur in patients receiving COLUMVI. Premedicate
before each dose, and initiate treatment with the COLUMVI step-up
dosing schedule to reduce the risk of CRS. Withhold COLUMVI until
CRS resolves or permanently discontinue based on severity. (2.1, 2.2,
2.3, 2.4, 5.1)--------------------------- INDICATIONS AND USAGE ---------------------------COLUMVI is a bispecific CD20-directed CD3 T-cell engager indicated forthe treatment of adult patients with relapsed or refractory diffuse large B-cell
lymphoma, not otherwise specified (DLBCL, NOS) or large B-cell lymphoma(LBCL) arising from follicular lymphoma, after two or more lines of systemic
therapy.
This indication is approved under accelerated approval based on response rateand durability of response. Continued approval for this indication may becontingent upon verification and description of clinical benefit in aconfirmatory trial(s). (1)----------------------- DOSAGE AND ADMINISTRATION ---------------------- Pretreat with a single 1,000 mg dose of obinutuzumab intravenously 7days before initiation of COLUMVI (Cycle 1 Day 1). (2.2)
 Administer premedications as recommended. (2.3)
 Administer only as an intravenous infusion. (2.1)
 Recommended dosage (2.2):
Treatment Cyclea
Cycle 1

Day
Day 1
Day 8
Day 15
Day 1

Dose of COLUMVIObinutuzumab 1,000 mg
Step-up dose 1
2.5 mgStep-up dose 2
10 mg
30 mg

 Neurologic Toxicity: Can cause serious neurologic toxicity, including
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).
Monitor for neurologic toxicity; withhold or permanently discontinue
based on severity. (5.2)
 Serious Infections: Can cause serious or fatal infections. Monitor patientsfor signs and symptoms of infection and treat appropriately. (5.3)
 Tumor Flare: Can cause serious tumor flare reactions. Monitor patients at
risk for complications of tumor flare. (5.4)
 Embryo-Fetal Toxicity: May cause fetal harm. Advise females ofreproductive potential of the potential risk to the fetus and to use effective
contraception. (5.5, 8.1, 8.3)------------------------------ ADVERSE REACTIONS -----------------------------The most common (≥ 20%) adverse reactions, excluding laboratory
abnormalities, are cytokine release syndrome, musculoskeletal pain, rash,and fatigue. The most common (≥ 20%) Grade 3 to 4 laboratory
abnormalities are lymphocyte count decreased, phosphate decreased,
neutrophil count decreased, uric acid increased, and fibrinogen decreased.
(6.1)--------------------------USE IN SPECIFIC POPULATIONS---------------Lactation: Advise not to breastfeed. (8.2)
To report SUSPECTED ADVERSE REACTIONS, contact Genentech
at 1-888-835-2555 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION and Medication
Guide.

Cycle 2-12
Cycle = 21 days
 Administer in a facility equipped to monitor and manage CRS. (2.1, 2.2)
 Patients should be hospitalized for the 2.5 mg step-up dose and for
subsequent infusions as recommended. (2.1, 2.2)
 See Full Prescribing Information for instructions on preparation andadministration. (2.5)
aRevised: 6/2023

FULL PRESCRIBING INFORMATION: CONTENTS*
WARNING: CYTOKINE RELEASE SYNDROME
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Important Dosing Information
2.2 Recommended Dosage
2.3 Recommended Premedication and Prophylactic Medications
2.4 Dosage Modifications for Adverse Reactions
2.5 Preparation and Administration
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Cytokine Release Syndrome
5.2 Neurologic Toxicity
5.3 Serious Infections
5.4 Tumor Flare
5.5 Embryo-Fetal Toxicity
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
7 DRUG INTERACTIONS
8 USE IN SPECIFIC POPULATIONS

11
12

13
14
16
17

8.1 Pregnancy
8.2 Lactation
8.3 Females and Males of Reproductive Potential
8.4 Pediatric Use
8.5 Geriatric Use
DESCRIPTION
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
12.6 Immunogenicity
NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
CLINICAL STUDIES
14.1 Relapsed or Refractory DLBCL, NOS or LBCL Arising from
Follicular Lymphoma
HOW SUPPLIED/STORAGE AND HANDLINGPATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information are notlisted.

1
Reference ID: 5191969

FULL PRESCRIBING INFORMATIONWARNING: CYTOKINE RELEASE SYNDROME
Cytokine Release Syndrome (CRS), including serious or fatal reactions, can occur in patients receiving
COLUMVI. Premedicate before each dose, and initiate treatment with the COLUMVI step-up dosing
schedule to reduce the risk of CRS. Withhold COLUMVI until CRS resolves or permanently
discontinue based on severity [see Dosage and Administration (2.1, 2.2, 2.3, and 2.4) and Warnings andPrecautions (5.1)].
1
INDICATIONS AND USAGE
COLUMVI is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell
lymphoma, not otherwise specified (DLBCL, NOS) or large B-cell lymphoma (LBCL) arising from follicularlymphoma, after two or more lines of systemic therapy.
This indication is approved under accelerated approval based on response rate and durability of response [seeClinical Studies (14.1)]. Continued approval for this indication may be contingent upon verification anddescription of clinical benefit in a confirmatory trial(s).
2
2.1

2.2

DOSAGE AND ADMINISTRATION
Important Dosing Information
Administer only as an intravenous infusion through a dedicated infusion line that includes a sterile 0.2micron in-line filter.



COLUMVI should only be administered by a healthcare professional with immediate access toappropriate medical support, including supportive medications to manage severe CRS [see Dosage andAdministration (2.4)].

Ensure adequate hydration before administering COLUMVI.

Premedicate before each dose [see Dosage and Administration (2.3)].

Following pretreatment with obinutuzumab, administer COLUMVI according to the step-up dosing
schedule in Table 1 with appropriate premedication, including dexamethasone, to reduce the incidence
and severity of CRS [see Dosage and Administration (2.3)].

Due to the risk of CRS, patients should be hospitalized during and for 24 hours after completion of
infusion of step-up dose 1 (2.5 mg on Cycle 1 Day 8) [see Dosage and Administration (2.2) andWarnings and Precautions (5.1)].



Patients who experienced any grade CRS during step-up dose 1 should be hospitalized during and for 24hours after completion of step-up dose 2 (10 mg on Cycle 1 Day 15). CRS with step-up dose 2 can occur
in patients who did not experience CRS with step-up dose 1 [see Dosage and Administration (2.2) andWarnings and Precautions (5.1)].

For subsequent doses, patients who experienced Grade ≥ 2 CRS with their previous infusion should be
hospitalized during and for 24 hours after the completion of the next COLUMVI infusion.
Recommended Dosage

Pretreatment with Obinutuzumab
Pretreat all patients with a single 1,000 mg dose of obinutuzumab administered as an intravenous infusion on
Cycle 1 Day 1, 7 days prior to initiation of COLUMVI (see Table 1) to deplete the circulating and lymphoidtissue B cells.

Reference ID: 5191969

Obinutuzumab should be administered as an intravenous infusion at 50 mg/hour. The rate of infusion can be
escalated in 50 mg/hour increments every 30 minutes to a maximum of 400 mg/hour. Refer to the
obinutuzumab prescribing information for complete dosing information.
COLUMVI Step-up Dose Schedule
COLUMVI dosing begins with a step-up dose schedule. Following completion of pretreatment withobinutuzumab on Cycle 1 Day 1, administer COLUMVI as an intravenous infusion according to the step-up
dose schedule in Table 1. Administer premedications for each dose of COLUMVI as described in Table 3 [seeDosage and Administration (2.3)].
Table 1: COLUMVI Dosing Schedule (21-Day Treatment Cycles)
Treatment cycle
Cycle 1Day

Dose of COLUMVI

Duration of infusion

Obinutuzumab1

Day 1
Day 8

Step-up dose 1

2.5 mgDay 15

Step-up dose 2

10 mg

4 hours2

Cycle 2

Day 1

30 mg

4 hours2

Cycle 3 to 12

Day 1

30 mg

2 hours3

1

Refer to “Pretreatment with obinutuzumab” described above.
For patients who experience CRS with their previous dose of COLUMVI, the time of infusion may be extended up to 8 hours.
3
If the patient experienced CRS with the previous dose, the duration of infusion should be maintained at 4 hours.
2

Continue COLUMVI for a maximum of 12 cycles (inclusive of Cycle 1 step-up dosing) or until diseaseprogression or unacceptable toxicity, whichever occurs first.
Monitoring for Cytokine Release Syndrome [see Warnings and Precautions (5.1)]
Administer the COLUMVI infusions intravenously in a healthcare setting with immediate access to
medical support to manage CRS, including severe CRS.

For the first COLUMVI step-up dose (2.5 mg on Cycle 1 Day 8), patients should be hospitalized during
and for 24 hours after completion of the COLUMVI infusion.



Patients who experienced any grade CRS during step-up dose 1 should be hospitalized during and for 24hours after completion of step-up dose 2 (10 mg on Cycle 1 Day 15). CRS with step-up dose 2 can occur
in patients who did not experience CRS with step-up dose 1.

For subsequent infusions (30 mg on Day 1 of Cycle 2 or subsequent cycles), patients who experienced
Grade ≥ 2 CRS with their previous infusion should be hospitalized during and for 24 hours after
completion of the next COLUMVI infusion.

For monitoring after delayed or missed doses of COLUMVI, follow the recommendations in Table 2.

Delayed or Missed Doses
If a dose of COLUMVI is delayed, restart therapy based on the recommendations made in Table 2, then resume
the treatment schedule accordingly.
For repeat of the 2.5 mg dose patients should be hospitalized during and for 24 hours after completion of the
COLUMVI infusion. For the repeat of the 10 mg dose, patients should be hospitalized during and for 24 hours
after completion of the COLUMVI infusion if any grade CRS occurred during the most recent 2.5 mg dose.

Reference ID: 5191969

Table 2: Recommendations for Restarting COLUMVI After Dose Delay
Last Dose
AdministeredTime Since Last
Dose Administered

Action for Next Dose(s)aObinutuzumab
pretreatment (Cycle
1 Day 1)≤ 2 weeksAdminister COLUMVI 2.5 mg (Cycle 1 Day 8)b, then resume
the planned treatment schedule.

> 2 weeks

Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1).
Then administer COLUMVI 2.5 mg (Cycle 1 Day 8)b andresume the planned treatment schedule.

COLUMVI 2.5 mg(Cycle 1 Day 8)≤ 2 weeksAdminister COLUMVI 10 mg (Cycle 1 Day 15)c, then resume
the planned treatment schedule.

> 2 to ≤ 4 weeks

Repeat COLUMVI 2.5 mg (Cycle 1 Day 8)b.
Then administer COLUMVI 10 mg (Cycle 1 Day 15)c andresume the planned treatment schedule.

> 4 weeks

Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day
1) and COLUMVI 2.5 mg (Cycle 1 Day 8)b.
Then administer COLUMVI 10 mg (Cycle 1 Day 15)c andresume the planned treatment schedule.


COLUMVI 10 mg(Cycle 1 Day 15)≤ 2 weeksAdminister COLUMVI 30 mg (Cycle 2 Day 1), then resume
the planned treatment schedule.

> 2 to ≤ 6 weeks

Repeat COLUMVI 10 mg (Cycle 1 Day 15).c
Then administer COLUMVI 30 mg (Cycle 2 Day 1) andresume the planned treatment schedule.

> 6 weeks

Repeat obinutuzumab 1,000 mg pretreatment (Cycle 1 Day 1),
COLUMVI 2.5 mg (Cycle 1 Day 8)b, and COLUMVI 10 mg(Cycle 1 Day 15)c.
Then administer COLUMVI 30 mg (Cycle 2 Day 1) andresume the planned treatment schedule.


COLUMVI 30 mg(Cycle 2 onwards)≤ 6 weeksAdminister COLUMVI 30 mg, then resume the planned
treatment schedule.

> 6 weeks

Repeat the Cycle 1 regimen described in Table 1:
obinutuzumab 1,000 mg pretreatment (Day 1), COLUMVI
2.5 mg (Day 8)b, and COLUMVI 10 mg (Day 15)c.
Then administer COLUMVI 30 mg (Day 1 of next cycle)
and resume the planned treatment schedule.

aAdminister premedication as per Table 3 for all patients.
Patients should be hospitalized during and for 24 hours after completing infusion of the 2.5 mg dose.
cPatients should be hospitalized during and for 24 hours after completing infusion of the 10 mg dose if CRS occurred during
the most recent 2.5 mg dose.
b

2.3

Recommended Premedication and Prophylactic Medications

Premedication
Administer the following premedications to reduce the risk of CRS and infusion-related reactions [seeWarnings and Precautions (5.1)].

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Table 3: Premedications to be Administered for COLUMVI Infusion
Day of Treatment
Cycle

Cycle 1, Day 8 andDay 15;
Cycle 2;
Cycle 3

Patients requiring
premedication

All patients

All patients
All subsequentinfusionsPatients who
experienced any grade
CRS with the previous
dose*

Premedication

Administration

Dexamethasone 20 mg
intravenously*

Completed at least 1 hourprior to COLUMVI
infusion.

Acetaminophen 500 mg to 1,000
mg orally

At least 30 minutes before
COLUMVI infusion.

Antihistamine (diphenhydramine 50
mg orally or intravenously or
equivalent)Completed at least 30
minutes before COLUMVI
infusion.

Acetaminophen 500 mg to 1,000
mg orally

At least 30 minutes before
COLUMVI infusion.

Antihistamine (diphenhydramine 50
mg orally or intravenously or
equivalent)Completed at least 30
minutes before COLUMVI
infusion.

Dexamethasone 20 mg
intravenously*

Completed at least 1 hourprior to COLUMVI
infusion.

If dexamethasone is not available, administer prednisone 100 mg, prednisolone 100 mg, or methylprednisolone 80 mg
intravenously.

Tumor Lysis Syndrome Prophylaxis
Before starting COLUMVI, administer anti-hyperuricemics to patients at risk of tumor lysis syndrome, ensure
adequate hydration status, and monitor as appropriate [see Adverse Reactions (6.1)].
Antiviral Prophylaxis
Before starting COLUMVI, consider initiation of antiviral prophylaxis to prevent herpes virus reactivation.
Consider prophylaxis for cytomegalovirus infection in patients at increased risk [see Warnings and Precautions(5.3)].
Pneumocystis jirovecii Pneumonia (PJP)
Consider PJP prophylaxis prior to starting COLUMVI in patients at increased risk [see Warnings andPrecautions (5.3)].
2.4

Dosage Modifications for Adverse Reactions

No dosage reduction for COLUMVI is recommended.
Cytokine Release Syndrome
Identify CRS based on clinical presentation [see Warnings and Precautions (5.1)]. Evaluate for and treat othercauses of fever, hypoxia, and hypotension.
If CRS is suspected, withhold COLUMVI and manage according to the recommendations in Table 4 andcurrent practice guidelines. Administer supportive care for CRS, which may include intensive care for severe or
life-threatening cases.

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Table 4: Recommendations for Management of Cytokine Release Syndrome
GradeaGrade 1

Presenting Symptoms
Temperature ≥ 100.4°F (38°C)

ActionsbGrade 2bTemperature ≥ 100.4°F (38°C) with:

Hypotension not requiringvasopressorsand/orHypoxia requiring low-flow oxygenby nasal cannula or blow-by

Grade 3

Grade 4eTemperature ≥ 100.4°F (38°C)b with:

Hypotension requiring vasopressor(with or without vasopressin)

and/or

Hypoxia requiring high-flow
oxygene by nasal cannula, facemask, non-rebreather mask, or
Venturi mask

Temperature ≥ 100.4°F (38°C)b with:

Hypotension requiring multiple
vasopressors (excluding vasopressin)

Withhold COLUMVI and manage per current
practice guidelines.
o If symptoms resolve, restart infusion at a
slower rate.c
Ensure CRS symptoms are resolved for at least
72 hours before next dose.d
Consider slower infusion rate for next dose.
Withhold COLUMVI and manage per current
practice guidelines.
o If symptoms resolve, restart infusion at a
slower rate.c
Ensure CRS symptoms are resolved for at least 72
hours before next dose.d
For the next dose, consider a slower infusion rate,monitor more frequently, and consider
hospitalization.
For recurrent Grade 2 CRS, manage per Grade 3
CRS.
Withhold COLUMVI and manage per current
practice guidelines, which may include intensive
care.
Ensure CRS symptoms are resolved for at least 72
hours before next dose.d
Hospitalize for the next dose, monitor more
frequently, and consider a slower infusion rate.c
For recurrent Grade 3 CRS, permanently discontinue
COLUMVI.

Permanently discontinue COLUMVI and manage percurrent practice guidelines, which may include
intensive care.

and/orHypoxia requiring oxygen bypositive pressure (e.g., CPAP,
BiPAP, intubation, and mechanicalventilation)aAmerican Society for Transplantation and Cellular Therapy (ASTCT) 2019 consensus grading criteria.
Premedication may mask fever. Therefore if clinical presentation is consistent with CRS, follow these management
guidelines.
c
Duration of infusion may be extended up to 8 hours, as appropriate for that cycle (see Table 1).
dRefer to Table 2 for information on restarting COLUMVI after dose delays [see Dosage and Administration (2.2)].
e
Low-flow oxygen defined as oxygen delivered at < 6 L/minute, high-flow oxygen defined as oxygen delivered at ≥ 6
L/minute.
b

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Neurologic Toxicity, Including ICANSManagement recommendations for neurologic toxicity, including ICANS, is summarized in Table 5. At the firstsign of neurologic toxicity, including ICANS, consider neurology evaluation and withholding COLUMVI basedon the type and severity of neurotoxicity. Rule out other causes of neurologic symptoms. Provide supportive
therapy, which may include intensive care.
Table 5: Recommended Dosage Modification for Neurologic Toxicity (Including ICANS)
Adverse Reaction

Severity1,2

ActionsContinue COLUMVI and monitor neurologic
toxicity symptoms.



If ICANS, manage per current practice guidelines.

Withhold COLUMVI until neurologic toxicity
symptoms improve to Grade 1 or baseline.3, 4
Provide supportive therapy, and consider
neurologic evaluation.

Grade 1

Grade 2

Neurologic Toxicity1(including ICANS2)[see Warnings andPrecautions (5.2)]



If ICANS, manage per current practice guidelines.

Withhold COLUMVI until neurologic toxicity
symptoms improve to Grade 1 or baseline for atleast 7 days.4, 5
For Grade 3 neurologic events lasting more than 7days, consider permanently discontinuing
COLUMVI.
Provide supportive therapy, and consider
neurology evaluation.

Grade 3



If ICANS, manage per current practice guidelines.

Permanently discontinue COLUMVI.
Provide supportive therapy, which may include
intensive care, and consider neurology evaluation.



If ICANS, manage per current practice guidelines.

Grade 4

1

Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
Based on ASTCT 2019 grading for ICANS.
3
Consider the type of neurologic toxicity before deciding to withhold COLUMVI.
4
See Dosage and Administration (2.2) on restarting COLUMVI after dose delays.
5
Evaluate benefit-risk before restarting COLUMVI.
2

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Other Adverse Reactions
Table 6: Recommended Dosage Modifications for Other Adverse Reactions
Adverse Reactions1

Severity1

ActionsInfections [see Warnings
and Precautions (5.3)]

Grades 1 – 4Monitor for signs and symptoms of compression
or obstruction due to mass effect secondary totumor flare.

Monitor for signs and symptoms of compression
or obstruction due to mass effect secondary totumor flare, and institute appropriate treatment
including antihistamine and corticosteroids.
Withhold COLUMVI until tumor flare resolves.2

Grade 1
Tumor flare [see Warnings
and Precautions (5.4)]

Withhold COLUMVI in patients with active
infection until the infection resolves.2
For Grade 4, consider permanent discontinuationof COLUMVI.

Grades 2 – 4
Neutropenia

Absolute neutrophil countless than 0.5 x 109/LWithhold COLUMVI until absolute neutrophil
count is 0.5 x 109/L or higher.2

Thrombocytopenia

Platelet count less than 50 
x 109/L

Withhold COLUMVI until platelet count is 50 x
109/L or higher.2

Withhold COLUMVI until the toxicity resolves
to Grade 1 or baseline.2

Other Adverse Reactions[see Adverse Reactions(6.1)]
1
2

Grade 3 or higher

Based on NCI CTCAE, version 4.03.
See Dosage and Administration (2.2) on restarting COLUMVI after dose delays.

2.5

Preparation and Administration

PreparationParenteral drug products should be inspected visually for particulate matter and discoloration prior toadministration, whenever solution and container permit. COLUMVI is a colorless clear solution.
Discard the vial if the solution is cloudy, discolored, or contains visible particles.

Use aseptic technique when preparing the COLUMVI diluted solution for intravenous infusion.



Determine the dose, total volume of COLUMVI solution, and the number of COLUMVI vials needed(see Table 7).

Dilution

Withdraw the volume of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection from theinfusion bag according to Table 7 and discard.

Withdraw the required volume of COLUMVI from vial(s) using a sterile needle and syringe and diluteinto the infusion bag of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection according
to Table 7 to a final concentration of 0.1 mg/mL to 0.6 mg/mL. Discard any unused portion left in thevial.

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Table 7: Dilution of COLUMVI for infusion
Dose of COLUMVISize of infusion
bag

Volume of 0.9% Sodium Chloride
Injection or 0.45% Sodium Chloride
Injection to be withdrawn and discarded

Volume of COLUMVI to
be added in the infusionbag

2.5 mg50 mL

27.5 mL

2.5 mL

50 mL

10 mL

10 mL

100 mL

10 mL

10 mL

50 mL

30 mL

30 mL

100 mL

30 mL

30 mL

10 mg
30 mg



Gently invert infusion bag to mix the solution, in order to avoid excessive foaming. Do not shake.



Immediately use diluted COLUMVI solution. If not used immediately, the diluted solution can be
stored:o Refrigerated at 2°C to 8°C (36°F to 46°F) for up to 64 hours, oro At room temperature up to 25°C (77°F) for up to 4 hours.
o Do not freeze the diluted infusion solution.
o Discard diluted infusion solution if storage time exceeds these limits.

COLUMVI diluted with 0.9% Sodium Chloride Injection is compatible with intravenous infusion bags
composed of polyvinyl chloride (PVC), polyethylene (PE), polypropylene (PP) or non-PVC polyolefin. When
diluted with 0.45% Sodium Chloride Injection, COLUMVI is compatible with intravenous infusion bags
composed of PVC.
No incompatibilities have been observed with infusion sets with product-contacting surfaces of polyurethane(PUR), PVC, or PE, and in-line filter membranes composed of polyethersulfone (PES) or polysulfone.
COLUMVI Administration
Administer COLUMVI as an intravenous infusion only through a dedicated infusion line that includes asterile 0.2-micron in-line filter.



See Table 1 for duration of infusion. The maximum time for the administration of the diluted infusion
solution may be extended up to 8 hours (see Table 4).

Do not mix COLUMVI with other drugs.

3
DOSAGE FORMS AND STRENGTHS
Injection:


2.5 mg/2.5 mL (1 mg/mL) clear, colorless solution in a single-dose vial.



10 mg/10 mL (1 mg/mL) clear, colorless solution in a single-dose vial.

4
CONTRAINDICATIONS
None.

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55.1

WARNINGS AND PRECAUTIONS
Cytokine Release Syndrome

COLUMVI can cause serious and fatal cytokine release syndrome (CRS) [see Adverse Reactions (6.1)].
Among 145 patients who received COLUMVI, CRS occurred in 70%, with Grade 1 CRS developing in 52% of
all patients, Grade 2 in 14%, Grade 3 in 2.8%, and Grade 4 in 1.4%. The most common manifestations of CRS
included fever, tachycardia, hypotension, chills, and hypoxia.
CRS occurred in 56% of patients after the 2.5 mg dose of COLUMVI, 35% after the 10 mg dose, 29% after the
initial 30 mg target dose, and 2.8% after subsequent doses. With the first step-up dose of COLUMVI, themedian time to onset of CRS (from the start of infusion) was 14 hours (range: 5 to 74 hours). CRS after any
dose resolved in 98% of cases, with a median duration of CRS of 2 days (range: 1 to 14 days). Recurrent CRS
occurred in 34% of all patients. CRS can first occur with the 10 mg dose; of 135 patients treated with the 10 mg
dose of COLUMVI, 15 patients (11%) experienced their first CRS event with the 10 mg dose, of which 13
events were Grade 1, 1 event was Grade 2, and 1 event was Grade 3.
Administer COLUMVI in a facility equipped to monitor and manage CRS. Initiate therapy according to the
COLUMVI step-up dosing schedule to reduce the risk of CRS, administer pretreatment medications, and ensure
adequate hydration [Dosage and Administration (2.3)]. Patients should be hospitalized during and for 24 hours
after completing infusion of the 2.5 mg step-up dose. Patients who experienced any grade CRS during the 2.5
mg step-up dose should be hospitalized during and for 24 hours after completion of the 10 mg step-up dose. For
subsequent doses, patients who experienced Grade ≥ 2 CRS with the previous infusion should be hospitalized
during and for 24 hours after the next COLUMVI infusion [see Dosage and Administration (2.1 and 2.2)].
At the first sign of CRS, immediately evaluate patients for hospitalization, manage per current practiceguidelines, and administer supportive care; withhold or permanently discontinue COLUMVI based on severity[see Dosage and Administration (2.4)].
5.2

Neurologic Toxicity

COLUMVI can cause serious and fatal neurologic toxicity, including Immune Effector Cell-Associated
Neurotoxicity (ICANS) [see Adverse Reactions (6.1)].
Among 145 patients who received COLUMVI, the most frequent neurologic toxicities of any grade were
headache (10%), peripheral neuropathy (8%), dizziness or vertigo (7%), and mental status changes (4.8%,
including confusional state, cognitive disorder, disorientation, somnolence, and delirium). Grade 3 or higher
neurologic adverse reactions occurred in 2.1% of patients and included somnolence, delirium, and myelitis.
Cases of ICANS of any grade occurred in 4.8% of patients.
Coadministration of COLUMVI with other products that cause dizziness or mental status changes may increase
the risk of neurologic toxicity. Optimize concomitant medications and hydration to avoid dizziness or mental
status changes. Institute fall precautions as appropriate.
Monitor patients for signs and symptoms of neurologic toxicity, evaluate, and provide supportive therapy;
withhold or permanently discontinue COLUMVI based on severity [see Dosage and Administration (2.4)].
Evaluate patients who experience neurologic toxicity such as tremors, dizziness, or adverse reactions that may
impair cognition or consciousness promptly, including potential neurology evaluation. Advise affected patientsto refrain from driving and/or engaging in hazardous occupations or activities, such as operating heavy or
potentially dangerous machinery, until the neurologic toxicity fully resolves.
5.3

Serious Infections

COLUMVI can cause serious or fatal infections [see Adverse Reactions (6.1)].
Serious infections were reported in 16% of patients, including Grade 3 or 4 infections in 10%, and fatal
infections in 4.8% of patients. Grade 3 or higher infections reported in  2% of patients were COVID-19

Reference ID: 5191969

infection (6%), including COVID-19 pneumonia, and sepsis (4.1%). Febrile neutropenia occurred in 3.4% of
patients.
COLUMVI should not be administered to patients with an active infection. Administer antimicrobial
prophylaxis according to guidelines. Monitor patients before and during COLUMVI treatment for infection andtreat appropriately. Withhold or consider permanent discontinuation of COLUMVI based on severity [seeDosage and Administration (2.4)].
5.4

Tumor Flare

COLUMVI can cause serious tumor flare [see Adverse Reactions (6.1)]. Manifestations include localized pain
and swelling at the sites of the lymphoma lesions and/or dyspnea from new pleural effusions.
Tumor flare was reported in 12% of patients who received COLUMVI, including Grade 2 tumor flare in 4.8%of patients and Grade 3 tumor flare in 2.8%. Recurrent tumor flare occurred in two (12%) of the affectedpatients. Most tumor flare events occurred during Cycle 1, with a median time to first onset of 2 days (range: 1
to 16 days) after the first dose of COLUMVI. The median duration was 3.5 days (range: 1 to 35 days).
Patients with bulky tumors or disease located in close proximity to airways or a vital organ should be monitored
closely during initial therapy. Monitor for signs and symptoms of compression or obstruction due to mass effectsecondary to tumor flare, and institute appropriate treatment. Withhold COLUMVI until tumor flare resolves[see Dosage and Administration (2.4)].
5.5

Embryo-Fetal Toxicity

Based on its mechanism of action, COLUMVI may cause fetal harm when administered to a pregnant woman.
Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use
effective contraception during treatment with COLUMVI and for 1 month after the last dose [see Use inSpecific Populations (8.1, 8.3)].
6
ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:

Cytokine Release Syndrome [see Warnings and Precautions (5.1)]



Neurologic Toxicity [see Warnings and Precautions (5.2)]



Serious Infections [see Warnings and Precautions (5.3)]

Tumor Flare [see Warnings and Precautions (5.4)]

6.1

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in theclinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may notreflect the rates observed in practice.
Relapsed or Refractory DLBCL, NOS or LBCL Arising from Follicular Lymphoma
Study NP30179
The safety of COLUMVI was evaluated in Study NP30179, a multi-cohort, multicenter, single-arm clinical trialthat included 154 adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or morelines of systemic therapy [see Clinical Studies (14.1)]. The trial required an ECOG performance status of 0 or 1,
absolute neutrophil count ≥ 1,500/µL, platelet count ≥ 75,000/µL independent of transfusion, serum creatinine ≤1.5 x upper limit of normal (ULN) or creatinine clearance (CLcr) ≥ 50 mL/min, and hepatic transaminases ≤ 3 x
ULN. The trial excluded patients with active or previous central nervous system (CNS) lymphoma or CNS
disease, acute infection, recent infection requiring intravenous antibiotics, or prior allogeneic hematopoietic
stem cell transplantation (HSCT).

Reference ID: 5191969

Patients received pretreatment with a single dose of obinutuzumab on Day 1 of Cycle 1 (seven days prior tostart of COLUMVI). Following premedication, COLUMVI was administered by intravenous infusion according
to the step-up dosing schedule with 2.5 mg on Day 8 of Cycle 1, and 10 mg on Day 15 of Cycle 1. Patients
received the 30 mg COLUMVI dose by intravenous infusion on Day 1 of subsequent cycles for a maximum of
12 cycles (including step-up dosing). Each cycle was 21 days. Patients were hospitalized during and for 24hours following completion of at least the first step-up dose.
Of the 154 patients who initiated study treatment, 145 received COLUMVI; nine patients (6%) did not receive
COLUMVI due to infection, progressive disease, or patient decision. Patients received a median of 5 cycles of
COLUMVI with 30% receiving all 12 cycles of COLUMVI.
Of patients who received COLUMVI, the median age was 66 years (range: 21 to 90 years); 66% were male;
77% were White, 4.8% were Asian, 1.4% were Black or African American, 6% were Hispanic or Latino. The
main diagnoses were DLBCL, NOS and LBCL arising from follicular lymphoma.
Serious adverse reactions occurred in 48% of patients who received COLUMVI. Serious adverse reactions in≥ 2% of patients included CRS, COVID-19 infection, sepsis, and tumor flare. Fatal adverse reactions occurred
in 5% of patients from COVID-19 infection (3.4%), sepsis (1.4%), and delirium (0.6%).
Adverse reactions led to permanent discontinuation of COLUMVI in 7% of patients, including from infection,delirium, neutropenia, and CRS. Adverse reactions led to dose interruptions of COLUMVI in 19% of patients,
most frequently (≥ 2%) from neutropenia and thrombocytopenia.
The most common (≥ 20%) adverse reactions, excluding laboratory terms, were CRS, musculoskeletal pain,
rash, and fatigue. The most common Grade 3 to 4 laboratory abnormalities (≥ 20%) were lymphocyte countdecreased, phosphate decreased, neutrophil count decreased, uric acid increased, and fibrinogen decreased.
Table 8 summarizes adverse reactions observed in Study NP30179.
Table 8: Select Adverse Reactions (≥ 10%) in Patients with Relapsed or Refractory LBCL Who
Received COLUMVI in Study NP30179
Adverse Reactions
Immune system disorders
Cytokine release syndrome
Musculoskeletal and connective tissue disorders
Musculoskeletal paina
General disorders
Fatigueb
Pyrexia
EdemacSkin and subcutaneous tissue disorders
Rashd
Gastrointestinal disorders
Constipation
Diarrhea
NauseaAbdominal paine
Neoplasms
Tumor flare
Neurologic Disorders
Headache

COLUMVI
N=145
All grades (%)
Grade 3 or 4 (%)
70

4.1

21

2.1

20
16
10

1.4
0
0

20

1.4

14
14
10
10

0
0
0
0

12

2.8

10

0

The table includes a combination of grouped and ungrouped terms. Adverse reactions were graded using NCI CTCAE version 4.03,
with the exception of CRS, which was graded per ASTCT consensus criteria in most cases.
aIncludes musculoskeletal pain, back pain, bone pain, flank pain, myalgia, neck pain, and pain in extremity.

Reference ID: 5191969

COLUMVI
N=145
All grades (%)
Grade 3 or 4 (%)

Adverse Reactionsb

Includes fatigue and asthenia.
Includes edema, edema peripheral, swelling face, and face edema.
dIncludes rash, rash pruritic, rash maculo-papular, dermatitis, dermatitis acneiform, dermatitis exfoliative, erythema, palmar
erythema, pruritus, and rash erythematous.
eIncludes abdominal pain, abdominal discomfort, and abdominal pain upper.
c

Clinically relevant adverse reactions occurring in < 10% of patients who received COLUMVI included
infusion-related reaction, peripheral neuropathy, pneumonia, mental status changes, vomiting, tumor lysis
syndrome, febrile neutropenia, upper respiratory tract infection, sepsis, herpes zoster infection, gastrointestinal
hemorrhage, tremor, and myelitis.
Table 9 summarizes laboratory abnormalities in Study NP30179.
Table 9: Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with
Relapsed or Refractory LBCL Who Received COLUMVI in Study NP30179
Laboratory Abnormality
Hematology
Lymphocytes decreased
Hemoglobin decreased
Neutrophils decreased
Platelets decreased
Chemistry
Fibrinogen decreased
Phosphate decreased
Sodium decreased
Calcium decreased
Gamma-glutamyl transferase increased
Potassium decreased
Uric acid increased

COLUMVIa
All Grades (%)

Grade 3 or 4 (%)

90
72
56
56

83
8
26b
8

84
69
49
48
33
32
23

21
28
7
2.1
9
6
23

a

The denominator used to calculate the rate varied from 137 to 145 based on the number of patients with a baseline value and at
least one post-treatment value.
b
Grade 4 neutrophil decrease occurred in 9% of patients.

7
DRUG INTERACTIONS
For certain CYP substrates where minimal concentration changes may lead to serious adverse reactions,monitor for toxicities or drug concentrations of such CYP substrates when coadministered with COLUMVI.
Glofitamab-gxbm causes the release of cytokines [see Clinical Pharmacology (12.2)] that may suppress theactivity of CYP enzymes, resulting in increased exposure of CYP substrates. Increased exposure of CYP
substrates is more likely to occur after the first dose of COLUMVI on Cycle 1 Day 8 and up to 14 days after the
first 30 mg dose on Cycle 2 Day 1 and during and after CRS [see Warnings and Precautions (5.1)].
8
8.1

USE IN SPECIFIC POPULATIONS
Pregnancy

Risk Summary

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Based on its mechanism of action COLUMVI may cause fetal harm when administered to a pregnant woman[see Clinical Pharmacology (12.1)]. There are no available data on the use of COLUMVI in pregnant women toevaluate for a drug-associated risk. No animal reproductive and developmental toxicity studies have been
conducted with glofitamab-gxbm.
Glofitamab-gxbm causes T-cell activation and cytokine release; immune activation may compromise pregnancy
maintenance. In addition, based on expression of CD20 on B cells and the finding of B-cell depletion in nonpregnant animals, glofitamab-gxbm can cause B-cell lymphocytopenia in infants exposed to glofitamab-gxbm
in-utero. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, COLUMVI has thepotential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to thefetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage inclinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
8.2

Lactation

Risk Summary
There are no data on the presence of glofitamab-gxbm in human milk or the effects on the breastfed child or
milk production. Because human IgG is present in human milk, and there is potential for glofitamab-gxbm
absorption leading to B-cell depletion, advise women not to breastfeed during treatment with COLUMVI andfor 1 month after the last dose of COLUMVI.
8.3

Females and Males of Reproductive Potential

COLUMVI may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations(8.1)].
Pregnancy Testing
Verify pregnancy status in females of reproductive potential prior to initiating COLUMVI.
Contraception
Females
Advise female patients of reproductive potential to use effective contraception during treatment with
COLUMVI and for 1 month after the last dose of COLUMVI [see Use in Specific Populations (8.1)].
8.4

Pediatric Use

The safety and efficacy of COLUMVI in pediatric patients have not been established.
8.5

Geriatric Use

Of the 145 patients with relapsed or refractory LBCL who received COLUMVI in study NP30179, 55% were
65 years of age or older, and 23% were 75 years of age or older. There was a higher rate of fatal adverse
reactions, primarily from COVID-19, in patients 65 years of age or older compared to younger patients [seeAdverse Reactions (6.1)]. No overall differences in efficacy were observed between patients 65 years of age orolder and younger patients.
11
DESCRIPTION
Glofitamab-gxbm is a bispecific CD20-directed CD3 T-cell engager. It is a recombinant humanized anti-CD20
anti-CD3ɛ bispecific immunoglobulin G1 (IgG1) monoclonal antibody produced in Chinese hamster ovary(CHO) cells. Glofitamab-gxbm has an approximate molecular weight of 197 kDa.
COLUMVI (glofitamab-gxbm) injection is a sterile, preservative-free, colorless, clear solution supplied insingle-dose vials for intravenous infusion.

Reference ID: 5191969

COLUMVI is supplied in 2.5 mg/2.5 mL and 10 mg/10 mL single-dose vials at a concentration of 1 mg/mL.
Each mL of solution contains 1 mg glofitamab-gxbm, histidine (0.63 mg), histidine hydrochloride monohydrate(3.34 mg), methionine (1.49 mg), polysorbate 20 (0.5 mg), sucrose (82.15 mg), and Water for Injection, USP, at
pH 5.5.
12
12.1

CLINICAL PHARMACOLOGY
Mechanism of Action

Glofitamab-gxbm is a bispecific antibody that binds to CD20 expressed on the surface of B cells, and to CD3
receptor expressed on the surface of T cells. Glofitamab-gxbm causes T-cell activation and proliferation,
secretion of cytokines, and the lysis of CD20-expressing B cells. Glofitamab-gxbm showed anti-tumor activity
in vivo in mouse models of DLBCL.
12.2

Pharmacodynamics

Circulating B Cell Count
Peripheral B cell counts decreased to undetectable levels (< 5 cells/microliter) in 86.5% of patients by Cycle 1
Day 7 after obinutuzumab pretreatment of 1,000 mg on Cycle 1 Day 1, and in 88.2% of patients by Cycle 1 Day
10 after the first glofitamab-gxbm dose of 2.5 mg on Cycle 1 Day 8.
Cytokine Concentrations
Plasma concentrations of cytokines (IL-2, IL-6, IL-10, TNF-α, and IFN-γ) were measured and transientelevation of cytokines was observed at doses of 0.045 mg and above. After administration of the recommended
dosage of COLUMVI, the highest elevation of cytokines was generally observed within 6 hours after the firstglofitamab-gxbm dose of 2.5 mg on Cycle 1 Day 8. The elevated cytokine levels generally returned to baseline
within 48 hours after the first 30 mg dose on Cycle 2 Day 1.
12.3

Pharmacokinetics

The pharmacokinetics of glofitamab-gxbm was determined following pretreatment with a single dose of
obinutuzumab of 1,000 mg and the pharmacokinetic parameters are presented as geometric mean (CV%) unlessotherwise specified. Glofitamab-gxbm exposure increased dose-proportionally over the dose range from 0.005
to 30 mg (0.000167 to 1 time the recommended treatment dosage). Glofitamab-gxbm exposure parameters are
summarized in Table 10 for the approved recommended dosage of COLUMVI.
Table 10: Exposure Parameters of Glofitamab-gxbm Following Pretreatment with a Single Dose of
Obinutuzumab of 1,000 mg
First full 30 mg dose
Steady state1 30 mg dose

AUCtau (day∙mcg/mL)
44.5 (55%)
48.6 (33%)

Cmax (mcg/mL)
9.41 (27%)
9.44 (26%)

Ctrough (mcg/mL)
0.52 (83%)
0.59 (67%)

Data presented as geometric mean (CV%). AUCtau = area under the concentration-time curve over one 21-day cycle;
Cmax = maximum glofitamab-gxbm concentration; Ctrough = glofitamab-gxbm concentration prior to next dose; CV = geometriccoefficient of variation.
1
Steady state values are approximated at Cycle 6 (week 18).

Distribution
The glofitamab-gxbm total volume of distribution is 5.6 L (24%).
Elimination
At steady state, the glofitamab-gxbm terminal half-life is 7.6 days (24%) and the clearance is 0.617 L/day(33%).

Reference ID: 5191969

Metabolism
Glofitamab-gxbm is expected to be metabolized into small peptides by catabolic pathways.
Specific Populations
No clinically significant changes in the pharmacokinetics of glofitamab-gxbm were observed based on age(21 to 90 years), body weight (31 to 148 kg), sex, mild to moderate renal impairment (CLcr 30 to < 90 mL/min
as estimated by Cockcroft-Gault formula) and mild hepatic impairment (total bilirubin > ULN to ≤ 1.5 x ULN
or AST > ULN).
The effects of severe renal impairment (CLcr 15 to < 30 mL/min), end-stage renal disease (CLcr < 15 mL/min),or moderate to severe hepatic impairment (total bilirubin > 1.5 x ULN and any AST), and race/ethnicity on thepharmacokinetics of glofitamab-gxbm are unknown.
Drug Interaction Studies
No clinical studies evaluating the drug interaction potential of glofitamab-gxbm have been conducted.
12.6 Immunogenicity
The observed incidence of antidrug antibodies (ADA) is highly dependent on the sensitivity and specificity of
the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the study
described below with the incidence of ADA in other studies, including those of glofitamab-gxbm.
During treatment in Study NP30179 (up to 9 months) [see Clinical Studies (14.1)], using an enzyme-linked
immunosorbent assay (ELISA), the incidence of anti-glofitamab antibody formation was 1.1% (5/448) inpatients treated with COLUMVI. Because of the low occurrence of ADAs, the effect of these antibodies on thepharmacokinetics, pharmacodynamics, safety, and/or effectiveness of glofitamab-gxbm is unknown.
13
13.1

NONCLINICAL TOXICOLOGY
Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity or genotoxicity studies have been conducted with glofitamab-gxbm.
Fertility studies have not been conducted with glofitamab-gxbm.
14
14.1

CLINICAL STUDIES
Relapsed or Refractory DLBCL, NOS or LBCL Arising from Follicular Lymphoma

The efficacy of COLUMVI was evaluated in Study NP30179 (NCT03075696), an open-label, multicenter,
multicohort, single-arm clinical trial that included patients with relapsed or refractory LBCL after two or morelines of systemic therapy. The trial required an ECOG performance status of 0 or 1, absolute neutrophil count ≥1,500/µL, platelet count ≥ 75,000/µL independent of transfusion, serum creatinine ≤ 1.5 x ULN or CLcr ≥ 50
mL/min, and hepatic transaminases ≤ 3 x ULN. The trial excluded patients with active or previous CNS
lymphoma or CNS disease, acute infection, recent infection requiring intravenous antibiotics, or prior allogeneic
HSCT.
Following pretreatment with obinutuzumab on Cycle 1 Day 1, patients received COLUMVI by intravenous
infusion, starting with a 2.5 mg step-up dose on Cycle 1 Day 8, followed by a 10 mg step-up dose on Cycle 1
Day 15, then 30 mg on Cycle 2 Day 1 and on Day 1 of each subsequent cycle. The cycle length was 21 days.
COLUMVI was administered for up to 12 cycles unless patients experienced progressive disease or
unacceptable toxicity.
The efficacy population consists of 132 patients with de novo DLBCL, NOS (80%) or LBCL arising fromfollicular lymphoma (20%) who received at least one dose of COLUMVI. The median age was 67 years(range: 21 to 90 years), 64% were male, 77% were White, 4.5% were Asian, 0.8% were Black or African
American, 5% were Hispanic or Latino. The median number of prior lines of systemic therapy was 3 (range: 2

Reference ID: 5191969

to 7). Most patients (83%) had refractory disease to the last therapy, 55% had primary refractory disease, 30%
had received CAR-T cell therapy, and 19% had received autologous HSCT.
Efficacy was based on objective response rate (ORR) and duration of response (DOR), as determined by an
Independent Review Committee (IRC) using the 2014 Lugano criteria.
Efficacy results are summarized in Table 11. The median time to first response was 42 days (range: 31 to 178days). Among responders, the estimated median follow-up for DOR was 11.6 months.
Table 11: IRC-Assessed Efficacy in Patients with Relapsed or Refractory DLBCL, NOS or LBCL Arisingfrom Follicular Lymphoma
COLUMVI
N=132

Outcome per IRC
Overall Response Rate, n (%)

74 (56)(95% CI)(47, 65)

Complete Response, n (%)

57 (43)(95% CI)(35, 52)

Partial Response, n (%)

17 (13)(95% CI)(8, 20)Duration of ResponseaN = 74bMedian DOR, months (95% CI)

18.4 (11.4, NE)b

68.5 (56.7, 80.3)

9-month estimate, % (95% CI)

CI = confidence interval; NE = not estimablea
From date of first response (PR or CR) until disease progression or death due to any cause.
b
Kaplan-Meier estimate.

16
HOW SUPPLIED/STORAGE AND HANDLINGCOLUMVI (glofitamab-gxbm) injection is a sterile, preservative-free, colorless, clear solution for intravenous
infusion.
COLUMVI is supplied as:
Carton Contents

NDC

One 2.5 mg/2.5 mL (1 mg/mL) single-dose vial

NDC 50242-125-01

One 10 mg/10 mL (1 mg/mL) single-dose vial

NDC 50242-127-01

Store refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze. Do notshake.
17
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Cytokine Release Syndrome
Inform patients of the risk of CRS. Advise patients to seek immediate medical attention if they experience signs
and symptoms of CRS (fever, hypoxia, hypotension, chills and tachycardia) [see Warnings and Precautions(5.1)].
Provide patients with the Patient Wallet Card that they should carry with them at all times. This card describes
symptoms of CRS which, if experienced, should prompt the patient to seek immediate medical attention.

Reference ID: 5191969

Neurologic Toxicity
Discuss the signs and symptoms associated with neurologic toxicity, including ICANS, headache, peripheral
neuropathy, dizziness, or mental status changes. Advise patients to immediately contact their healthcare
provider if they experience any signs or symptoms of neurologic toxicity. Advise patients who experience
neurologic toxicity that impairs consciousness to refrain from driving or operating heavy or potentially
dangerous machinery until neurologic toxicity resolves [see Warnings and Precautions (5.2)].
Serious Infections
Advise patients that COLUMVI can cause serious infections. Advise patients to notify their healthcare provider
immediately if they develop any signs of infection (e.g., fever, chills, weakness) [see Warnings and Precautions(5.3)].
Tumor Flare
Inform patients of the potential risk of tumor flare reaction and to report any signs and symptoms associatedwith this event (e.g., localized pain and swelling) to their healthcare provider for evaluation [see Warnings andPrecautions (5.4)].
Embryo-Fetal Toxicity
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform theirhealthcare provider if they are pregnant or become pregnant. Advise females of reproductive potential to use
effective contraception during treatment with COLUMVI and for 1 month after the last dose [see Warnings andPrecautions (5.5) and Use in Specific Populations (8.1, 8.3)].
Advise women not to breastfeed while receiving treatment with COLUMVI and for 1 month after the last dose[see Use in Specific Populations (8.2)].
COLUMVITM [glofitamab-gxbm]
Manufactured by:
Genentech, Inc.
A Member of the Roche Group
1 DNA WaySouth San Francisco, CA 94080-4990
U.S. License No.: 1048

Reference ID: 5191969

COLUMVITM is a trademark of
Genentech, Inc.
©2023 Genentech, Inc. All rights reserved.

MEDICATION GUIDECOLUMVITM (ko-loom-vee)(glofitamab-gxbm)
injection, for intravenous infusion
What is the most important information I should know about COLUMVI?
COLUMVI can cause Cytokine Release Syndrome (CRS), a serious side effect that is common during treatment with
COLUMVI, and can also be serious and lead to death.
 Call your healthcare provider or get emergency medical help right away if you develop any signs or symptomsof CRS, including:o dizziness or light-headedness
o fever of 100.4°F (38°C) or higher
o trouble breathingo chills or shaking
o shortness of breatho fast or irregular heartbeat
 Due to the risk of CRS, you will receive COLUMVI on a “step-up dosing schedule”.
o A single dose of a medicine called obinutuzumab will be given to you on the first day of your first treatment cycle(Day 1 of Cycle 1).
o You will start the COLUMVI step-up dosing schedule a week after the obinutuzumab dose. The step-up dosing
schedule is when you receive smaller “step-up” doses of COLUMVI on Day 8 and Day 15 of Cycle 1. This is to help
reduce your risk of CRS. You should be hospitalized during your infusion and for 24 hours after receiving the firststep-up dose on Day 8. You should be hospitalized during your infusion and for 24 hours after receiving the second
step-up dose on Day 15 if you experienced CRS during the first step-up dose.
o You will receive your first full dose of COLUMVI a week after the second step-up dose (this will be Day 1 of Cycle2).
o If your dose of COLUMVI is delayed for any reason, you may need to repeat the “step-up dosing schedule”.
o If you had more than mild CRS with your previous dose of COLUMVI, you should be hospitalized during and for 24hours after receiving your next dose of COLUMVI.
o Before each dose of COLUMVI, you will receive medicines to help reduce your risk of CRS and infusion-related
reactions.
o See “How will I receive COLUMVI?” for more information about how you will receive COLUMVI.
 Your healthcare provider will monitor you for CRS during treatment with COLUMVI and may treat you in a hospital if
you develop signs and symptoms of CRS. Your healthcare provider may temporarily stop or completely stop yourtreatment with COLUMVI if you have severe side effects.
 Carry the COLUMVI Patient Wallet Card with you at all times and show it to all of your healthcare providers.
The COLUMVI Patient Wallet Card lists the signs and symptoms of CRS you should get emergency medical help forright away.
See “What are the possible side effects of COLUMVI?” for more information about side effects.
What is COLUMVI?
COLUMVI is a prescription medicine used to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) or
large B-cell lymphoma (LBCL) that has come back (relapsed) or that did not respond to previous treatment (refractory), andwho have received 2 or more prior treatments for their cancer.
It is not known if COLUMVI is safe and effective in children.
Before receiving COLUMVI, tell your healthcare provider about all of your medical conditions, including if you: have an infection
 have kidney problems
 are pregnant or plan to become pregnant. COLUMVI may harm your unborn baby.
Females who are able to become pregnant:o Your healthcare provider should do a pregnancy test before you start treatment with COLUMVI.
o You should use effective birth control (contraception) during treatment and for 1 month after your last dose of
COLUMVI. Talk to your healthcare provider about what birth control method is right for you during this time.
o Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment
with COLUMVI.
 are breastfeeding or plan to breastfeed. It is not known if COLUMVI passes into your breastmilk. Do not breastfeed
during treatment and for 1 month after your last dose of COLUMVI.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter
medicines, vitamins, and herbal supplements.
How will I receive COLUMVI?
 COLUMVI will be given to you by your healthcare provider by infusion through a needle placed in your vein
(intravenous infusion).
 Your COLUMVI treatment schedule is divided into cycles that are 21 days (3 weeks) long.

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

On Day 1 of Cycle 1, your healthcare provider will give you a single dose of a medicine called obinutuzumab by
intravenous infusion. You will then receive COLUMVI on Day 8 and Day 15 of Cycle 1. Starting with Cycle 2, you will
receive COLUMVI 1 time every three weeks.

Your healthcare provider will decide how many treatment cycles you will receive of COLUMVI. See “What is the mostimportant information I should know about COLUMVI?” for more information about how you will receive COLUMVI.
What should I avoid while receiving COLUMVI?
Do not drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, shaking(tremors), sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. Thesemay be signs and symptoms of neurologic problems.
See “What are the possible side effects of COLUMVI?” for more information about signs and symptoms of neurologic
problems.
What are the possible side effects of COLUMVI?
COLUMVI may cause serious side effects, including: Cytokine Release Syndrome. See “What is the most important information I should know about COLUMVI?” Neurologic problems. COLUMVI can cause serious neurologic problems that may lead to death. Your healthcare
provider will monitor you for neurologic problems during treatment with COLUMVI. Your healthcare provider may also
refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you
develop any signs or symptoms of neurologic problems, including:o headacheo memory problems
o confusion and disorientationo numbness, tingling, or weakness of the hands or feeto dizzinesso difficulty paying attention or understanding thingso shaking (tremors)o trouble speakingo sleepiness Serious infections. COLUMVI can cause serious infections that may lead to death. Your healthcare provider will
monitor you for signs and symptoms of infection and treat you as needed. Tell your healthcare provider right away if you
develop any signs of infection, including: fever, chills, weakness, cough, shortness of breath, or sore throat.
 Growth in your tumor or worsening of tumor related problems (tumor flare). Tell your healthcare provider if you
get any of these signs or symptoms of tumor flare:o tender or swollen lymph nodeso pain or swelling at the site of the tumoro chest paino cougho trouble breathingYour healthcare provider may temporarily stop or completely stop treatment with COLUMVI if you develop certain side
effects.
The most common side effects of COLUMVI include: CRS, muscle and bone pain, rash, and tiredness.
The most common severe abnormal lab test results with COLUMVI include: decreased white blood cells, decreased
phosphate (an electrolyte), increased uric acid levels, and decreased fibrinogen (a protein that helps with blood clotting).
These are not all the possible side effects of COLUMVI.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about the safe and effective use of COLUMVI.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask yourhealthcare provider or pharmacist for information about COLUMVI that is written for health professionals.
What are the ingredients in COLUMVI?
Active ingredient: glofitamab-gxbm
Inactive ingredients: histidine, histidine hydrochloride monohydrate, methionine, polysorbate 20, sucrose, and Water for
injection.
Manufactured by: Genentech, Inc., A Member of the Roche Group, 1 DNA Way, South San Francisco, CA 94080-4990
U.S. License No.: 1048
For more information, go to www.COLUMVI.com or call 1-877-436-3683.
This Medication Guide has been approved by the U.S. Food and Drug Administration.

Reference ID: 5191969

Issued: 6/2023