Brexucabtagene autoleucel for BTKi-naive relapsed/refractory mantle cell lymphoma: primary analysis of ZUMA-2 Cohort 3

Brexu-cel is an autologous anti-CD19 CAR T-cell therapy approved for adults with R/R MCL in the US, and after ≥2 lines of prior therapy, including a BTKi in the EU. Approval was based on the ZUMA-2 Cohort 1 (NCT02601313) study in which brexu-cel demonstrated a 93% objective response rate (ORR) and 67% complete response (CR) rate in patients with R/R MCL and prior BTKi therapy (N=60). Here we report the primary results of ZUMA-2 Cohort 3, brexu-cel in patients with BTKi-naive R/R MCL. Adults received brexu-cel at 2×106 anti-CD19 CAR T cells/kg. The primary endpoint was ORR assessed by independent radiology review committee (IRRC). As of November 26, 2023, 95 patients were enrolled, and 86 received brexu-cel; median follow-up was 15.5 months. The primary endpoint was met, with a 91% ORR (95% CI, 82.5-95.9, P<.0001; N=86) and a CR rate of 73% (95% CI, 62.6-82.2). Estimated 12-month progression-free survival (PFS), duration of response (DOR), and overall survival (OS) rates were 75%, 80% and 90%, respectively. Among 95 enrolled patients, the ORR was 82%, the CR rate was 66%, and the 12-month PFS and OS rates (95% CI) were 73% (62.1-80.8) and 85% (75.6-90.7), respectively. Most patients (88%) experienced treatment-related Grade ≥3 adverse events, including 4 treatment-related Grade 5 events. Consistent with Cohort 1, brexu-cel demonstrated a high ORR and similar safety profile. These results support the continued use of brexu-cel in patients with R/R MCL, and consideration in some patients without prior BTKi therapy who have high-risk disease. This trial is registered at ClinicalTrials.gov as #NCT04880434.