On June 15, 2023, the bispecific CD20-directed CD3 T-cell engager glofitamab-gxbm was granted accelerated approval for relapsed or refractory diffuse large B-cell lymphoma (DLBCL)–not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma after at least two lines of systemic therapy.1
Supporting Efficacy Data
Approval was supported by findings in Study NP30179 (ClinicalTrials.gov identifier NCT03075696), in which 132 patients received glofitamab. Overall, 80% of patients had relapsed or refractory DLBCL–not otherwise specified, and 20% had LBCL arising from follicular lymphoma. Patients had received a median of three prior lines of systemic therapy (range = two to seven).
An objective response on independent review committee assessment was observed in 74 patients (56%, 95% confidence interval [CI] = 47%–65%), with a complete response in 57 (43%). The estimated median duration of response after a median follow-up of 11.6 months among responders was 18.4 months (95% CI = 11.4 months to not estimable), with an estimated 68.5% of responses ongoing at 9 months.
How It Is Used
After a single 1,000-mg dose of obinutuzumab on cycle 1 day 1 to deplete circulating and lymphoid tissue B cells, glofitamab is given via intravenous infusion according to a step-up dosing schedule of 2.5 mg on day 8 and 10 mg on day 15 of cycle 1, followed by 30 mg on day 1 of each subsequent 21-day cycle for a maximum of 12 cycles. The agent must be administered in a facility equipped to monitor and manage cytokine-release syndrome; patients should be hospitalized for the 2.5 mg step-up dose and subsequently as described in the product labeling. The product labeling provides instructions for premedication.
Safety Profile
Safety data are from 145 patients who received glofitamab in Study NP30179. The most common adverse events of any grade were cytokine-release syndrome (70%), musculoskeletal pain (21%), rash (20%), and fatigue (20%). The most common grade 3 or 4 adverse events included cytokine-release syndrome (4.1%) and tumor flare (2.8%). The most common grade 3 or 4 laboratory abnormalities were decreases in lymphocytes (83%), phosphate (28%), neutrophils (26%), and fibrinogen (21%) and increased uric acid (23%).
Serious adverse events occurred in 48% of patients, most commonly (≥ 2%) cytokine-release syndrome, COVID-19 infection, sepsis, and tumor flare. Adverse events led to discontinuation of treatment in 7% (including infection, delirium, neutropenia, and cytokine-release syndrome). Fatal adverse events occurred in 5% of patients, including COVID-19 infection (3.4%), sepsis (1.4%), and delirium (0.6%).
Glofitamab-gxbm has a boxed warning for cytokine-release syndrome. The agent also has warnings or precautions for neurologic toxicity, including immune effector cell–associated neurotoxicity; serious infections; tumor flare; and embryofetal toxicity. Patients should be advised not to breastfeed while receiving glofitamab.
REFERENCE
1. Columvi (glofitamab-gxbm) injection, for intravenous use, prescribing information, Genentech, Inc, June 2023. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761309s000lbl.pdf. Accessed June 29, 2023.
