FDA Approves Brexu-Cel for Relapsed/Refractory MCL

The FDA has granted traditional approval to brexucabtagene autoleucel (Tecartus; brexu-cel) for the treatment of adult patients with relapsed/refractory mantle cell lymphoma (MCL).¹

The decision to convert the brexu-cel indication to a full approval was supported by data from the phase 2 ZUMA-2 trial (cohorts 1 and 2, NCT02601313; cohort 3, NCT04880434), including confirmatory findings from cohort 3, in which the treatment elicited durable responses and had a manageable safety profile in patients with MCL that was relapsed or refractory following at least 1 line of therapy and who had not previously received a Bruton tyrosine kinase (BTK) inhibitor.

Among evaluable patients in cohort 3 (n = 86), at a median follow-up of 23.0 months, the overall response rate (ORR) was 91% (95% CI, 82.5%-95.9%), the complete response (CR) rate was 79% (95% CI, 69.0%-87.1%), and the median duration of response (DOR) was not reached (NR; 95% CI, 26.2 months-not evaluable [NE]).^1,2 Notably, patients in this cohort had received a median of 1 prior line of therapy.

Among evaluable patients in cohort 1 (n = 60), at a median follow-up of 8.6 months, the ORR was 87% (95% CI, 75%-94%), the CR rate was 62% (95% CI, 48%-74%), and the median DOR was NR (95% CI, 8.6 months-NE). Patients in this cohort had received a median of 3 prior lines of therapy.

“The full approval of brexu-cel in relapsed or refractory MCL, along with the inclusion of cohort 3 data in the label, reinforces our confidence in the overall profile of brexu-cel,” Michael Wang, MD, lead investigator of ZUMA-2 and a professor in the Department of Lymphoma and Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, stated in a news release.¹ “The cohort 3 results showed high response rates, including deep remissions, in patients who were BTK inhibitor–naive, with a manageable safety profile consistent with prior experience. These data provide important information to help guide treatment decisions in the relapsed or refractory setting for appropriate patients.”

What was the design of the ZUMA-2 trial?

This single-arm, open-label, multicenter trial enrolled adult patients with relapsed/refractory MCL across 3 cohorts:

• Cohorts 1 and 2 (n = 82): patients who had previously received a maximum of 5 lines of therapy, including bendamustine- or anthracycline-containing chemotherapy, a BTK inhibitor, and an anti-CD20 antibody
• Cohort 3: patients who had previously received a maximum of 5 lines of therapy and were naive to BTK inhibition

ORR served as the primary end point across the study.

Patients underwent leukapheresis, followed by a single infusion of brexu-cel.² Ninety percent of patients received brexu-cel at 2 x 10⁶ chimeric antigen receptor–positive T cells per kg.

What were the safety outcomes with brexu-cel in relapsed/refractory MCL in ZUMA-2?

Safety findings from a pooled population of cohorts 1 through 3 (n = 168) showed a CRS rate of 93%, including grade 3 or higher cytokine release syndrome (CRS) in 12% of patients.^1,2 The median time to CRS onset was 4 days, and the median duration was 7 days.

The rate of neurologic events was 80%, and 33% of patients had grade 3 or higher events. The median time to onset of neurologic events was 6 days, and the median duration was 19 days.

The rate of any-grade infections was 63%, including grade 3 or higher infections in 33% of patients.

In cohort 3 specifically, 65% of patients experienced serious adverse effects, the most common of which included the following: nonventricular arrhythmia, tachycardia, pyrexia, CRS, unspecified pathogen infections, viral infections, bacterial infections, fungal infections, musculoskeletal pain, motor dysfunction, encephalopathy, aphasia, tremor, seizure, delirium, hypoxia, hypotension, hemorrhage, and thrombosis.

“The full approval of [brexu-cel] for adult [patients] with relapsed or refractory MCL reflects meaningful progress,” Gallia Levy, MD, PhD, senior vice president and global head of development at Kite, added in the news release.¹ “For those whose cancer has returned, the data support [brexu-cel] as a second-line treatment option with the potential to deliver long-term remission.”

References

1. US FDA grants full approval of Kite’s Tecartus for adult patients with relapsed or refractory mantle cell lymphoma. News release. Gilead Sciences, Inc. April 2, 2026. Accessed April 2, 2026. https://www.gilead.com/company/company-statements/2026/us-fda-grants-full-approval-of-kite-tecartus-for-adult-patients-with-relapsed-or-refractory-mantle-cell-lymphoma
2. Tecartus. Prescribing Information. Kite Pharma, Inc; April 2026. Accessed April 2, 2026. https://www.gilead.com/-/media/files/pdfs/medicines/oncology/tecartus/tecartus-pi.pdf