FDA grants full approval to brexucabtagene autoleucel for R/R MCL

On April 2, 2026, the U.S. Food and Drug Administration (FDA) granted traditional approval to brexucabtagene autoleucel (brexu-cel), an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for the treatment of adult patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL), converting the previous accelerated approval to a full approval. This full approval expands the brexu-cel indication to include patients who have not received a Bruton’s tyrosine kinase inhibitor (BTKi) after ≥1 prior line of therapy.

Full approval was based on results from the phase II ZUMA-2 study (NCT02601313), which enrolled patients with R/R MCL after ≤5 prior lines of therapy. Patients in Cohorts 1 and 2 had previously received BTKi therapy (n = 82) and patients in Cohort 3 were BTKi-naïve (n = 86). The overall response rate (ORR) in Cohort 3 was 91%, with 79% of patients demonstrating a complete response (CR). In Cohort 1, the ORR was 87% and CR rate was 62%. Pooled safety data (n = 168) showed cytokine release syndrome (CRS), neurologic toxicities, and infections occurred in 93%, 80%, and 63% of patients, respectively, with 12%, 33%, and 33% being Grade ≥3. 

The FDA has included a boxed warning for brexu-cel regarding potentially life-threatening CRS and neurologic toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS) and secondary hematologic malignancies.