The U.S. Food and Drug Administration (FDA) has granted traditional approval to the chimeric antigen receptor (CAR) T-cell therapy brexucabtagene autoleucel (Tecartus) for adult patients with relapsed or refractory mantle cell lymphoma (MCL). The full approval now includes efficacy, safety, and pharmacokinetic data from cohort 3 of the ZUMA-2 study (ClinicalTrials.gov identifier NCT05537766) in patients whose disease becomes relapsed or refractory after one or more lines of therapy and who are Bruton’s tyrosine kinase (BTK) inhibitor–naive.
This action converts the relapsed or refractory MCL indication to full approval based on the totality of evidence from ZUMA-2, including confirmatory data from cohort 3, which demonstrated high response rates, durable efficacy outcomes, and a manageable safety profile consistent with prior experience. This milestone fulfills the postmarketing requirement for verification and description of clinical benefit in a confirmatory trial under the FDA’s Accelerated Approval pathway for brexucabtagene autoleucel in relapsed/refractory MCL.
“The full approval of [brexucabtagene autoleucel] in relapsed or refractory MCL, along with the inclusion of cohort 3 data in the label, reinforces our confidence in the overall profile of brexucabtagene autoleucel,” said Michael Wang, MD, ZUMA-2 lead investigator and Professor in the Department of Lymphoma and Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. “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.”
MCL is a rare form of non-Hodgkin lymphoma that arises from cells originating in the “mantle zone” of the lymph node and predominantly affects men over the age of 60. Approximately 33,000 people worldwide are diagnosed with MCL each year. MCL is highly aggressive following relapse, with many patients’ disease progressing following therapy.
More From ZUMA-2
ZUMA-2 is a single-arm, open-label, multicenter study evaluating brexucabtagene autoleucel in adult patients with relapsed or refractory MCL. Cohorts 1 and 2 evaluated the therapy in patients who had previously received up to five lines of therapy, including anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody, and a BTK inhibitor. Cohort 3 evaluated brexucabtagene autoleucel in patients who had received up to five prior lines of therapy and were BTK inhibitor–naive. A total of 82 patients were treated in cohorts 1 and 2 and 86 patients were treated in cohort 3. The primary endpoint across the study was objective response rate per the Lugano Classification (2014), as assessed by an Independent Radiologic Review Committee.
The objective response rate in cohort 1 was 87%; in cohort 3, it was 91%. The complete remission rate was 62% vs 79%; in both cohorts, the median duration of response was not reached (the median follow-up for duration of response at the time of the primary analysis was 8.6 months in cohort 1 vs 23.0 months in cohort 3).
In the updated U.S. Prescribing Information, MCL safety data are pooled across cohorts 1–3 (n = 168). In this pooled MCL population, cytokine-release syndrome (CRS) occurred in 93% of patients, including grade ≥ 3 CRS in 12%; the median time to onset was 4 days and the median duration was 7 days. Neurologic events occurred in 80% of patients, including grade ≥ 3 neurologic events in 33%; the median time to onset was 6 days and the median duration was 19 days. Infections of any grade occurred in 63% of patients, including grade ≥ 3 infections in 33%. In cohort 3, serious adverse reactions occurred in 65% of patients. The most common serious adverse reactions (occurring in > 2% of patients) were 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.
