FDA Grants Full Approval to Brexu-Cel in R/R Mantle Cell Lymphoma

The FDA has granted traditional approval to brexucabtagene autoleucel (Tecartus; brexu-cel) for treatment of adult patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL), converting the agent’s previous accelerated approval to a full approval.¹

Brexu-cel, an autologous CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy, initially earned accelerated approval from the FDA in July 2020 based on data from cohort 1 of the phase 2 ZUMA-2 study (NCT02601313), which included patients who were previously exposed to Bruton tyrosine kinase (BTK) inhibitors.² The continued approval, which was contingent upon confirmatory data demonstrating clinical benefit, now incorporates data from cohort 3 of the study (NCT04880434), which enrolled 95 patients who are R/R after 1 or more lines of therapy and who are BTK inhibitor-naive.

Notably, the therapy demonstrated success in its primary end point of objective response rate (ORR) per the 2014 Lugano classification, exhibiting high rates of response and durability. In the primary analysis conducted separately from cohorts 1 and 2, the ORR was 91% (95% CI, 82.5%-95.9%) among the 86 patients treated with a single infusion of brexu-cel, with a complete remission (CR) rate of 79%.³ Median duration of response was not reached at the time of analysis.

The transition to full approval provides further validation for the use of the CAR T-cell therapy in the second-line setting or later for MCL. Before the advent of CAR T-cell therapy, patients who progressed after BTK inhibitor therapy had a median overall survival of approximately 6 to 10 months. The durability data suggest that brexu-cel may significantly alter the natural history of the disease for a subset of patients.

The full approval also reinforces the importance of early referral to authorized treatment centers for patients showing signs of resistance to BTK inhibitors. As the therapeutic landscape for MCL continues to evolve with the introduction of bispecific antibodies and next-generation BTK inhibitors, brexu-cel remains a cornerstone for achieving deep, durable remissions in R/R disease.

“The full approval of brexu-cel in [R/R 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, professor at The University of Texas MD Anderson Cancer Center and ZUMA-2 lead investigator, 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.”

ZUMA-2 Study Design

The ZUMA-2 trial is a single-arm, multicenter, open-label study evaluating the efficacy and safety of brexu-cel in a total of 168 adult patients with R/R MCL across 3 cohorts.^4,5 Cohorts 1 and 2 enrolled patients who had been treated with up to 5 prior regimens including a BTK inhibitor, while cohort 3 enrolled those who had not received prior therapy with a BTK inhibitor.

The primary end point was ORR, defined as the combined rate of CR and partial response as assessed by an independent radiology review committee using the Lugano classification. Secondary end points included DOR, progression-free survival, overall survival, and safety assessments.

Safety Considerations and Boxed Warnings

The safety profile of brexu-cel remains consistent with previous reports. Brexu-cel’s prescribing information includes a boxed warning for cytokine release syndrome (CRS), secondary hematologic malignancies, and neurological toxicities, also known as immune effector cell-associated neurotoxicity syndrome (ICANS).

Pooling the cohorts together, CRS occurred in 93%, with grade 3 or higher CRS occurring in 12%. The median time to onset was 4 days. Neurological toxicities occurred in 80% of patients, with grade 3 or higher events occurring in 33%. The rate of any-grade infections was 63%, with 33% experiencing a grade 3 or higher event.

In cohort 3, the most common serious adverse reactions (incidence ≥20%) included nonventricular arrhythmias, tachycardias, 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.

Due to these risks, brexu-cel was initially made available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). However, in June 2025, the FDA eliminated the REMS program for several CAR-T therapies including brexu-cel, expanding access to patients.

REFERENCES

1. U.S. FDA grants full approval of Kite’s Tecartus® for adult patients with relapsed or refractory mantle cell lymphoma. News release. Gilead Sciences. April 2, 2026. Accessed April 2, 2026. https://tinyurl.com/3dbjt2m9

2. FDA approves brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma. News release. United States Food and Drug Administration. July 27, 2020. Accessed April 2, 2026. https://tinyurl.com/5xfp8eaf

3. van Meerten T, Kersten MJ, Iacoboni G, et al. Brexucabtagene autoleucel for BTKi-naive relapsed/refractory mantle cell lymphoma: primary analysis of ZUMA-2 cohort 3. Blood. 2026;147(12):1302-1314. doi:10.1182/blood.2025029734

4. Study of brexucabtagene autoleucel (KTE-X19) in participants with relapsed/refractory mantle cell lymphoma (cohort 3) (ZUMA-2). ClinicalTrials.gov. Updated November 17, 2025. Accessed April 2, 2026. https://clinicaltrials.gov/study/NCT04880434

5. Study of brexucabtagene autoleucel (KTE-X19) in participants with relapsed/refractory mantle cell lymphoma (cohort 1 and cohort 2) (ZUMA-2). ClinicalTrials.gov. Updated March 18, 2026. Accessed April 2, 2026. https://clinicaltrials.gov/study/NCT02601313