On June 15, 2023, the FDA accelerated the approval of glofitamab-gxbm (Columvi; Genentech), a bispecific CD20-directed CD3 T-cell engager, for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), or large B-cell lymphoma (LBCL) arising from follicular lymphoma after ≥2 lines of systemic therapy. The FDA granted this application priority review and fast track designation.
The approval was based on results from the phase 1/2 NP30179 study, an open-label, multicenter, single-arm clinical trial of 132 patients with relapsed or refractory DLBCL, NOS (80% of patients), or LBCL arising from follicular lymphoma (20% of patients) who had received ≥2 previous lines of systemic therapy (median, 3; range, 2-7). Patients with active or previous central nervous system lymphoma or disease were excluded from the trial.
Objective response rate (ORR) and duration of response (DOR) were the main efficacy measures. The ORR was 56% (95% confidence interval [CI], 47-65), with 43% having complete responses. Responders had an estimated median follow-up of 11.6 months, with an estimated median DOR of 18.4 months (95% CI, 11.4-not estimable). The 9-month Kaplan-Meier estimate for DOR was 68.5% (95% CI, 56.7-80.3), and the median time to response was 42 days.
The prescribing information for glofitamab has a boxed warning for serious or fatal cytokine release syndrome (CRS); other warnings and precautions include neurologic toxicity including immune effector cell–associated neurotoxicity syndrome (ICANS), serious infections, and tumor flare. Of 145 patients with relapsed or refractory LBCL evaluated for safety, 70% had CRS (grade ≥3 CRS, 4.1%), 4.8% had ICANS, 16% had serious infections, and 12% had tumor flare.
The most common (≥20%) adverse reactions, excluding laboratory abnormalities, were CRS, musculoskeletal pain, rash, and fatigue. The most common (≥20%) grade 3/4 laboratory abnormalities were decreased lymphocytes, phosphate, neutrophils, and fibrinogen, and increased uric acid.
Prior to glofitamab administration, a single 1000-mg dose of obinutuzumab (Gazyva; Genentech) is given on cycle 1 day 1 to deplete circulating and lymphoid-tissue B cells, after which glofitamab is administered via intravenous infusion on a step-up dosing schedule (2.5 mg on day 8 of cycle 1 and 10 mg on day 15 of cycle 1). Then 30 mg is given on day 1 of each subsequent cycle for a maximum of 12 cycles. Each cycle is 21 days.
