Brexucabtagene autoleucel for BTKi-naive relapsed/refractory mantle cell lymphoma: primary analysis of ZUMA-2 cohort 3
Tom van Meerten, Marie José Kersten, Gloria Iacoboni, Georg Hess, Pim Mutsaers, Alejandro Martín García-Sancho, Andre Goy, Eva Giné, Brian T. Hill, Wen-Kai Weng, Patrick M. Reagan, Krish Patel, Ahmed Galal, Charles Herbaux, Robin Sanderson, Edouard Forcade, Max S. Topp, Roch Houot, Dan Zheng, Wangshu Zhang, Justyna Kanska, Rhine R. Shen, Rita Damico Khalid, Ioana Kloos, Martin Dreyling, Michael L. Wang
Abstract
Abstract Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for adults with relapsed/refractory (R/R) mantle cell lymphoma (MCL) based on the ZUMA-2 cohort 1 (ClinicalTrials.gov identifier: 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 previous 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 per kilogram. The primary end point was ORR assessed by independent radiology review committee (IRRC). As of 26 November 2023, 95 patients were enrolled, and 86 received brexu-cel; median follow-up was 15.5 months. The primary end point was met, with a 91% ORR (95% confidence interval [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, 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 previous BTKi therapy who have high-risk disease. This trial was registered at clinicaltrials.gov as #NCT04880434.