Skip To Main Content
Patient and Caregiver Site

COLUMVI™ safety profile1

Select adverse reactions (≥10%) in patients with relapsed or refractory LBCL who received COLUMVI in study NP30179
Adverse Reactions COLUMVI
N=145
  All Grades (%) Grade 3 to 4 (%)
Immune system disorders
Cytokine release syndrome		 70 4.1
Musculoskeletal and connective tissue disorders
Musculoskeletal pain*		 21 2.1
General disorders
Fatigue†
Pyrexia
Edema‡		 20
16
10		 1.4
0
0
Skin and subcutaneous tissue disorders
Rash§		 20 1.4
Gastrointestinal disorders
Constipation
Diarrhea
Nausea
Abdominal pain||		 14
14
10
10		 0
0
0
0
Neoplasms
Tumor flare		 12 2.8
Neurologic disorders
Headache		 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.

*Includes musculoskeletal pain, back pain, bone pain, flank pain, myalgia, neck pain, and pain in extremity.
†Includes fatigue and asthenia.
‡Includes edema, edema peripheral, swelling face, and face edema.
§Includes rash, rash pruritic, rash maculo-papular, dermatitis, dermatitis acneiform, dermatitis exfoliative, erythema, palmar erythema, pruritus, and rash erythematous.
‖Includes abdominal pain, abdominal discomfort, and abdominal pain upper.

<COLUMVI> Call Out Icon
4.1% rate (n=6/145) of Grade 3 or 4 CRS was observed

Clinically relevant adverse reactions occurring in <10% of patients who received COLUMVI included infusion-related reaction, mental status changes, vomiting, tumor lysis syndrome, febrile neutropenia, pneumonia, upper respiratory tract infection, sepsis, herpes zoster infection, gastrointestinal hemorrhage, tremor, and myelitis.

  • 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

Safety: laboratory abnormalities

Select laboratory abnormalities (≥20%) that worsened from baseline in patients with relapsed or refractory LBCL who received COLUMVI in STUDY NP30179
Laboratory Abnormality COLUMVI
  All Grades (%) Grade 3 or 4 (%)
Hematology
Lymphocytes decreased
Hemoglobin decreased
Neutrophils decreased
Platelets decreased		 90
72
56
56		 83
8
26#
8
Chemistry
Fibrinogen decreased
Phosphate decreased
Sodium decreased
Calcium decreased
Gamma-glutamyl transferase increased
Potassium decreased
Uric acid increased		 84
69
49
48
33
32
23		 21
28
7
2.1
9
6
23

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.
#Grade 4 neutrophil decrease occurred in 9% of patients.

NEXT: CRS Rates

ASTCT=American Society for Transplantation and Cellular Therapy; CTCAE=Common Terminology for Adverse Events; CRS=cytokine release syndrome; LBCL=large B-cell lymphoma; NCI=National Cancer Institute.

Explore the CRS grading tool

Get information on identifying CRS based on clinical presentation.

Explore Now
View dose modifications for CRS

Review the COLUMVI™ CRS grading (based on ASTCT) and management recommendation table.

Learn More

Important Safety Information & Indication

Indication

COLUMVI (glofitamab-gxbm) is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified (DLBCL), 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 rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

BOXED WARNING

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.

Warnings and Precautions

Cytokine Release Syndrome (CRS)

COLUMVI can cause serious and fatal CRS.

Among the 145 patients who received COLUMVI, CRS occurred in 70%, with Grade 1 CRS developing in 52% of patients, Grade 2 in 14%, Grade 3 in 2.8% of patients, 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, the median 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. 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 their previous infusion should be hospitalized during and for 24 hours after the next COLUMVI infusion.

At the first sign of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care; withhold or permanently discontinue COLUMVI based on severity.

Neurologic Toxicity

COLUMVI can cause serious neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity (ICANS).

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.

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 patients to 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.

Serious Infections

COLUMVI can cause serious or fatal infections.

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% patients were COVID-19 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 and treat appropriately. Withhold or consider permanent discontinuation of COLUMVI based on severity.

Tumor Flare

COLUMVI can cause serious tumor flare. Manifestations included 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 affected patients. 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 effect secondary to tumor flare, and institute appropriate treatment. Withhold COLUMVI until tumor flare resolves.

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.

Most Common Adverse Reactions

The most common (≥ 20%) adverse reactions, excluding laboratory abnormalities, are CRS (70%), musculoskeletal pain (21%), rash (20%), and fatigue (20%). The most common Grade 3 to 4 laboratory abnormalities (≥ 20%) are lymphocyte count decreased (83%), phosphate decreased (28%), neutrophil count decreased (26%), uric acid increased (23%), and fibrinogen decreased (21%).

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 that may suppress the activity 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.

Use in Specific Populations

Lactation
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 and for 1 month after the last dose of COLUMVI.

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. No overall differences in efficacy were observed between patients 65 years of age or older and younger patients.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see the COLUMVI full Prescribing Information for additional Important Safety Information, including BOXED WARNING.

    • COLUMVI. Prescribing Information. Genentech, Inc.

      COLUMVI. Prescribing Information. Genentech, Inc.

    • Dickinson MJ, Carlo-Stella C, Morschhauser F, et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2022;387(24):2220-2231. doi:10.1056/NEJMoa2206913.

      Dickinson MJ, Carlo-Stella C, Morschhauser F, et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2022;387(24):2220-2231. doi:10.1056/NEJMoa2206913.

    • Bacac M, Colombetti S, Herter S, et al. CD20-TCB with obinutuzumab pretreatment as next-generation treatment of hematologic malignancies. Clin Cancer Res. 2018;24(19):4785-4797. doi: 10.1158/1078-0432.CCR-18-0455.

      Bacac M, Colombetti S, Herter S, et al. CD20-TCB with obinutuzumab pretreatment as next-generation treatment of hematologic malignancies. Clin Cancer Res. 2018;24(19):4785-4797. doi: 10.1158/1078-0432.CCR-18-0455.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.5.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed July 7, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.5.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed July 7, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org.

    • Data on file. Genentech, Inc.

      Data on file. Genentech, Inc.