Brexucabtagene Autoleucel Efficacy, Toxicity in MCL ‘Consistent’ with ZUMA-2 Data

Brexucabtagene autoleucel in the standard-of-care setting for relapsed or refractory mantle cell lymphoma (MCL) showed efficacy and toxicity “consistent” with ZUMA-2 results, according to a recent study.

Yucai Wang, MD, PhD, of Mayo Clinic, and colleagues conducted the research and published its results in the Journal of Clinical Oncology.

Brexucabtagene autoleucel, an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy, was approved for relapsed or refractory MCL based on data from the single-arm phase II ZUMA-2 trial. The trial showed a best overall response rate of 91%, with a 65% complete response (CR) rate.

The study included 189 patients who underwent leukapheresis with an intent to manufacture commercial brexucabtagene autoleucel for relapsed or refractory MCL. Leukapheresis took place at 16 US institutions between August 2020 and December 2021. Of those patients, 89% received an infusion of brexucabtagene autoleucel. The study’s investigators collected patient data for analyses of responses, outcomes, and toxicities as per standard guidelines.

Most of the patients who underwent leukapheresis (79%) would not have been eligible for the ZUMA-2 trial. The best overall response rate was 90%, while the CR rate was 82%. The estimated six-month progression-free survival (PFS) rate was 69% (95% CI, 61 to 75), and the estimated one-year PFS rate was 59% (95% CI, 51 to 66).

The one-year non-relapse mortality rate was 9.1%, “primarily because of infections,” according to Dr. Wang and colleagues. Cytokine release syndrome of grade 3 or higher occurred in 8% of patients, while neurotoxicity of grade 3 or higher occurred in 32%.

A univariate analysis showed high-risk simplified MCL international prognostic index, high Ki-67, TP53 aberration, complex karyotype, and blastoid/pleomorphic variant were with shorter PFS after brexucabtagene autoleucel infusion.

In an intention-to-treat univariable analysis, patients who were exposed to bendamustine within 24 months before leukapheresis had shorter PFS and overall survival after leukapheresis.

“In the standard-of-care setting, the efficacy and toxicity of [brexucabtagene autoleucel] were consistent with those reported in the ZUMA-2 trial,” Dr. Wang and colleagues concluded. “Tumor-intrinsic features of MCL, and possibly recent bendamustine exposure, may be associated with inferior efficacy outcomes.”

Reference

Wang Y, Jain P, Locke FL, et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US lymphoma CAR T consortium. J Clin Oncol. 2023. doi:10.1200/JCO.22.01797