FDA Approves Brexucabtagene Autoleucel for R/R Mantle Cell Lymphoma
Key Clinical Summary:
- Design/Population: Based on results from the phase 2 ZUMA-2 study, the FDA approved brexucabtagene autoleucel for adult patients with relapsed/refractory mantle cell lymphoma, including those who are BTKi–naïve.
- Key Outcomes: High response rates were observed, including a 91% ORR and 79% complete remission rate in BTKi-naïve patients. Safety findings included high rates of CRS and neurologic events, consistent with prior CAR T-cell therapy experience.
- Clinical Relevance: These results support the use of brexucabtagene autoleucel as a treatment option for relapsed or refractory mantle cell lymphoma, including earlier-line settings. The approval reinforces the role of CAR T-cell therapy in this disease.
On April 2, 2026, the US Food and Drug Administration (FDA) approved brexucabtagene autoleucel (Tecartus®; Kite) for adult patients with relapsed/refractory mantle cell lymphoma (MCL), including those who are Bruton tyrosine kinase (BTK) inhibitor–naïve. This approval was based on results from the ZUMA-2 trial.
In this multicenter, single-arm study, 168 adult patients who had received up to 5 prior lines of therapy, including anthracycline- or bendamustine-containing chemotherapy and an anti-CD20 antibody were enrolled to receive 2 × 106 anti-CD19 CAR T-cells/kg of brexucabtagene autoleucel. Patients were either BTKi-exposed (cohorts 1/2; n = 82) or BTK inhibitor-naïve (cohort 3; n = 86). The primary end point was objective response rate (ORR), as assessed by independent radiologic review. Key secondary end points included duration of response and safety.
At analysis, the ORR was 87% in BTK inhibitor-exposed patients and 91% in the BTK inhibitor-naïve patients, with complete remission rates of 62% and 79%, respectively. Median duration of response was not reached across all cohorts. Pooled safety data identified that cytokine release syndrome was observed in 93% of patients, 12% of which were grade ≥3. Neurologic events occurred in 80% of patients, 33% of which grade ≥3. The median time to onset was 4 days for CRS and 6 days for neurologic events. Infections occurred in 63% of patients, 33% of which were grade ≥3.
Serious adverse reactions were reported in 65% of BTK inhibitor-naïve patients. The most common serious adverse reactions occurring in >2% of patients included non-ventricular arrhythmias, tachycardias, pyrexia, cytokine release syndrome, unspecified pathogen infections, viral infections, bacterial infections, fungal infections, musculoskeletal pain, motor dysfunction, encephalopathy, aphasia, tremor, seizure, delirium, hypoxia, hypotension, hemorrhage, and thrombosis.
The prescribing information includes a boxed warning for cytokine release syndrome, neurologic toxicities including immune effector cell–associated neurotoxicity syndrome, and secondary malignancies.
“The full approval of [brexucabtagene autoleucel] in relapsed or refractory mantle cell lymphoma, along with the inclusion of Cohort 3 data in the label, reinforces our confidence in the overall profile of [brexucabtagene autoleucel],” stated Michael Wang, MD, lead investigator of the ZUMA-2 trial, from MD Anderson Cancer Center, Houston, Texas. “These data provide important information to help guide treatment decisions in the relapsed or refractory setting for appropriate patients.”
Sources:
Gilead. U.S. FDA grants full approval of Kite’s Tecartus® for adult patients with relapsed or refractory mantle cell lymphoma. 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
Van Meerten T, Kersten MJ, Lacoboni G, et al. Brexucabtagene autoleucel for BTKi-naive relapsed/refractory mantle cell lymphoma: Primary analysis of ZUMA-2 cohort 3. Blood. Published online: March 19, 2026. doi:10.1182/blood.2025029734
