Glofitamab-gxbm, marketed as Columvi, has received accelerated approval for treating adult patients with relapsed or refractory diffuse large B-cell lymphoma (LBCL) not otherwise specified, or LBCL arising from follicular lymphoma, after two or more lines of systemic therapy. This approval, granted on June 15, 2023, is based on response rate and durability of response observed in the phase 1/2 NP30179 study (NCT03075696).
Efficacy Data from Phase 1/2 NP30179 Study
The accelerated approval of glofitamab-gxbm is supported by positive results from the phase 1/2 NP30179 study. In this study, glofitamab-gxbm was administered as a fixed course to 132 patients. The results showed that 56% of patients achieved a response, with a median duration of response of 18.4 months. Among those who responded, 68.5% continued to respond at 9 months, and 43% achieved a complete response (remission).
Mechanism of Action
Glofitamab-gxbm is a CD20xCD3 T-cell engaging bispecific antibody. Its unique 2:1 structural format targets one region that binds to the CD3 protein on T cells and two regions that bind to CD20, a protein found on both healthy and cancerous B cells. This dual-binding activity activates and redirects a patient’s T cells to engage and eliminate the targeted B cells by releasing cancer cell–killing proteins. It is important to note that this process can also harm healthy B cells.
Administration and Dosage
Glofitamab-gxbm is administered as a fixed-duration intravenous infusion through a dedicated infusion line with a 0.2-μm in-line filter. The treatment consists of a maximum of 12 cycles over approximately 8.5 months. The infusion duration varies, with cycles 1 and 2 administered over 4 hours and subsequent cycles over 2 hours.
The recommended dose includes a 1000-mg pretreatment dose of obinutuzumab on day 1 of cycle 1 to mitigate adverse effects. Subsequent glofitamab-gxbm doses are administered on day 8 (2.5 mg) and day 15 (10 mg) of cycle 1, followed by a full 30-mg dose on day 1 of cycles 2 to 12. Premedication with a corticosteroid, antipyretic, and antihistamine is required before each infusion to reduce the risk of cytokine release syndrome (CRS) and infusion-related reactions.
Managing Adverse Events
Glofitamab-gxbm carries a boxed warning for CRS, a potentially serious and fatal condition. Clinical trials reported CRS in 70% of patients, with 35% of cases occurring after the 10-mg dose and 29% after the initial 30-mg targeted dose. Patients exhibiting signs and symptoms of CRS should be evaluated for potential hospital admission and managed according to institutional guidelines.
Immune effector cell–associated neurotoxicity syndrome (ICANS) was also observed, with any-grade ICANS occurring in 4.8% of patients and grade 3 or higher in 2.1%. Patients should be monitored for neurotoxicity and advised to avoid hazardous activities. Treatment may be held or discontinued based on the severity of CRS/ICANS.
Other potential adverse effects include tumor lysis syndrome, tumor flare, rash, fatigue, laboratory test abnormalities, and infection. Patients with bulky tumors or disease near the airway or vital organs should be closely monitored during initial treatment for tumor flare.
Patient and Nurse Education
Patients should be educated about the risks of CRS and ICANS, with emphasis on recognizing early symptoms such as fever, tachycardia, hypotension, chills, hypoxia, headache, peripheral neuropathy, dizziness, and changes in mental status. Clear management pathways for CRS and ICANS should be established at treating facilities, and care teams must be prepared to provide streamlined, high-quality care.
Nurses administering glofitamab-gxbm should be aware that the median time of onset for CRS in clinical trials was 14 hours (range, 5-74), with resolution in 98% of patients within a median duration of 2 days (range, 1-14). Patients should carry a wallet card indicating their risk of CRS and be instructed to inform outside care teams of their treatment. Facilities administering glofitamab-gxbm must be equipped to manage CRS and ICANS, and anti–IL-6 therapy should be considered for grade 1 or higher CRS unresponsive to supportive therapy.
