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FDA Accelerated the Approval of Columvi for Selected Relapsed or Refractory Large B-Cell Lymphomas

June 2023 Vol 16, No 1 - FDA Approvals

On June 15, 2023, the FDA accelerated the approval of glofitamab-gxbm (Columvi; Genentech) for 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.

Glofitamab, a bispecific CD20-directed CD3 T-cell engager, is the first bispecific antibody with a fixed duration of treatment approved for patients with relapsed or refractory DLBCL.

This approval was based on the results of the phase 1/2 NP30179 study (NCT03075696), an open-label, multicenter, single-arm clinical trial in 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.

“Patients with relapsed or refractory diffuse large B-cell lymphoma may experience rapid progression of their cancer and often urgently need an effective treatment option that can be administered without delay,” said Krish Patel, MD, Director of the Lymphoma Program at the Swedish Cancer Institute in Seattle, WA, and a study investigator. “Experience from clinical trials demonstrates that Columvi can provide patients with relapsed or refractory diffuse large B-cell lymphoma a chance for complete remission with a fixed-duration immunotherapy and that such remissions can potentially be sustained after the end of their treatment.”

Before glofitamab administration, a single 1000-mg dose of obinutuzumab 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 are given on day 1 of each subsequent cycle for a maximum of 12 cycles. Each cycle is 21 days.

Only healthcare professionals should administer glofitamab, with appropriate medical support available to manage severe reactions, including CRS. Because of the risk for CRS, patients should be hospitalized during and for 24 hours after the first step-up dose, and if CRS of any grade occurs with the 2.5-mg dose, patients should also be hospitalized for the second step-up dose (10 mg on day 15 of cycle 1). For subsequent doses, patients who have grade ≥2 CRS with their previous infusion should be hospitalized during and for 24 hours after the completion of the next infusion.

Continued approval for this indication may be contingent on a confirmatory trial(s) that verifies and describes clinical benefit.

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Last modified: June 27, 2023