RX Road Map: Glofitamab-gxbm (Columvi)

For Whom Is This Drug Approved?

Glofitamab-gxbm is a CD20×CD3 T-cell engaging bispecific antibody approved for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (LBCL) not otherwise specified or LBCL arising from follicular lymphoma after 2 or more lines of systemic therapy. Glofitamab-gxbm received accelerated approval on June 15, 2023, based on response rate and durability of response in the phase 1/2 NP30179 study (NCT03075696). Continued approval for this indication is contingent upon verification of clinical benefit in a confirmatory trial.

What Efficacy Data Back It Up?

Accelerated approval was based on the positive results from the phase 1/2 NP30179 study where glofitamab-gxbm was given as a fixed course to 132 patients. Fifty-six percent of patients treated with glofitamab-gxbm achieved a response, with a median duration of response of 18.4 months. Of those who achieved a response, 68.5% continued to respond at 9 months; 43% of those treated with glofitamab-gxbm achieved a complete response (remission).

How It Works

Glofitamab-gxbm is a CD20×CD3 T-cell engaging bispecific antibody with a 2:1 structural format designed to target 1 region that binds to CD3 protein on the surface of T cells (an immune cell) and 2 regions that bind to CD20, a protein on the surface of B cells. The B cells are either healthy or cancerous. The dual-binding activities activate and redirect a patient’s T cells to engage and eliminate the targeted B cells by releasing cancer cell–killing proteins from the T cells. During this process, healthy B cells can also be harmed.

How It’s Administered

Glofitamab-gxbm is a fixed-duration intravenous infusion. It must be administered through a dedicated infusion line that includes a 0.2-μm in-line filter. It is administered for 13 infusions (a maximum of 12 cycles) or until disease progression or unacceptable toxicity. The duration of infusion varies. Glofitamab-gxbm is administered over 4 hours for cycles 1 and 2 and over 2 hours for cycles 3 to 12. Treatment is completed in approximately 8.5 months.

The Recommended Dose

Day 1 of cycle 1 consists of a single 1000-mg pretreatment dose of obinutuzumab, which may decrease the adverse effects of glofitamab-gxbm. On day 8 of cycle 1, patients receive a 2.5-mg glofitamab-gxbm step-up dose. On day 15 of cycle 1, patients receive a 10-mg glofitamab-gxbm step-up dose. Cycles 2 to 12 are 21-day cycles, with a full 30-mg glofitamab-gxbm dose on day 1. For all cycles, patients are premedicated on the day of infusion with a corticosteroid, an antipyretic, and an antihistamine to reduce the risk of cytokine release syndrome (CRS) and infusion-related reactions.

How to Manage Associated Adverse Events

Glofitamab-gxbm has a boxed warning for CRS, which can be serious and fatal. CRS occurred in 70% of patients in clinical trial findings. In those patients, 35% of cases occurred after the 10-mg dose, 29% after the initial 30-mg targeted dose, and 2.8% after subsequent doses. Patients presenting with signs and symptoms of CRS should be evaluated for potential hospital admission and care managed per institutional guidelines.

Immune effector cell–associated neurotoxicity syndrome (ICANS) was also observed. Cases of any-grade ICANS occurred in 4.8% of patients. Of those patients, grade 3 or higher ICANS occurred in 2.1% of patients. Patients should be monitored for signs and symptoms of neurotoxicity, provided supportive therapy if needed, and instructed to refrain from hazardous activities such as driving a car. Glofitamab-gxbm should be held or discontinued completely based on CRS/ICANS severity.

This drug may be associated with an elevated risk for tumor lysis syndrome in some patients. Patients at risk should be monitored for clinical presentation of tumor lysis—electrolytes, uric acid, and renal function—as clinically indicated.

Tumor flare is another serious adverse effect. This manifests as localized pain and swelling at the sites of lymphoma regions and/or dyspnea from new pleural effusions. Tumor flare was reported in 12% of clinical trial patients; 2.8% of cases were characterized as grade 3. Patients with bulky tumors or disease close to their airway or vital organs should be monitored closely during initial treatment and treated as necessary. Glofitamab-gxbm should be held until tumor flare resolves. Other common adverse effects include rash, fatigue, laboratory test abnormalities, and infection.

What to Inform Patients About to Start Treatment

Educate patients regarding the boxed warning and risk for CRS and ICANS. The most common symptoms of CRS are fever, tachycardia, hypotension, chills, and hypoxia. The most common symptoms of ICANS are headache, peripheral neuropathy, dizziness, and change in mental status. Patients should be informed to alert their care team at the earliest signs of CRS/ICANS. Clear pathways, including clear operational workflows, for the management of CRS and ICANS should be established at treating facilities, and care teams must be educated to provide streamlined, high-quality patient care. Care teams receiving patient symptom–related phone calls should be educated on the workflows established for proper patient referral and care escalation.

Advice for Nurses Who Administer This Agent

It is important to note the median time of onset for CRS in findings from clinical trials was 14 hours (range, 5-74) and that CRS resolved in 98% of patients, with a median duration of 2 days (range, 1-14). Ensure patients are given a wallet card regarding their risk of CRS while receiving this medication. Although patients should be instructed to stay close to their treatment facility for 24 hours after treatment, there is a chance a patient could present to an outside hospital. Patients presenting to an outside facility or emergency department must be educated to show their wallet card to the outside care team, as their treatment may need to be managed differently. Patients with signs and symptoms of CRS/ICANS must be rapidly evaluated by the care team. Consider administering anti–IL-6 therapy for grade 1 or higher CRS that is unresponsive to supportive therapy. Glofitamab-gxbm should only be administered in a facility equipped to manage CRS and ICANS.

How to Safely Handle This Drug

Glofitamab-gxbm should be administered by chemotherapy/biotherapy/immunotherapy-credentialed registered nurses with immediate access to medical support and supportive medications for the management of CRS.

Reference

Columvi. Prescribing information. Genentech; 2024. Accessed August 15, 2024. https://www.columvi-hcp.com/