Brexucabtagene Autoleucel for Relapsed or Refractory Mantle Cell Lymphoma in Standard-of-Care Practice: Results From the US Lymphoma CAR T Consortium

Authors

Yucai Wang
Preetesh Jain
Frederick L Locke
Matthew J Maurer
Matthew J Frank
Javier L Munoz
Saurabh Dahiya
Amer M Beitinjaneh
Miriam T Jacobs
Joseph P Mcguirk
Julie M Vose
Andre Goy
Charalambos Andreadis
Brian T Hill
Kathleen A Dorritie
Olalekan O Oluwole
Abhinav Deol
Jonas Paludo
Bijal Shah
Trent Wang
Rahul Banerjee
David B Miklos
Aaron P Rapoport
Lazaros Lekakis
Armin Ghobadi
Sattva S Neelapu
Yi Lin
Michael L Wang
Michael D Jain

Publication Date

5-10-2023

Journal

Journal of Clinical Oncology

Abstract

Purpose: Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory mantle cell lymphoma (MCL). This therapy was approved on the basis of the single-arm phase II ZUMA-2 trial, which showed best overall and complete response rates of 91% and 68%, respectively. We report clinical outcomes with brexu-cel in the standard-of-care setting for the approved indication.

Patients and methods: Patients who underwent leukapheresis between August 1, 2020 and December 31, 2021, at 16 US institutions, with an intent to manufacture commercial brexu-cel for relapsed/refractory MCL, were included. Patient data were collected for analyses of responses, outcomes, and toxicities as per standard guidelines.

Results: Of 189 patients who underwent leukapheresis, 168 (89%) received brexu-cel infusion. Of leukapheresed patients, 79% would not have met ZUMA-2 eligibility criteria. Best overall and complete response rates were 90% and 82%, respectively. At a median follow-up of 14.3 months after infusion, the estimates for 6- and 12-month progression-free survival (PFS) were 69% (95% CI, 61 to 75) and 59% (95% CI, 51 to 66), respectively. The nonrelapse mortality was 9.1% at 1 year, primarily because of infections. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 8% and 32%, respectively. In univariable analysis, high-risk simplified MCL international prognostic index, high Ki-67, TP53 aberration, complex karyotype, and blastoid/pleomorphic variant were associated with shorter PFS after brexu-cel infusion. Patients with recent bendamustine exposure (within 24 months before leukapheresis) had shorter PFS and overall survival after leukapheresis in intention-to-treat univariable analysis.

Conclusion: In the standard-of-care setting, the efficacy and toxicity of brexu-cel were consistent with those reported in the ZUMA-2 trial. Tumor-intrinsic features of MCL, and possibly recent bendamustine exposure, may be associated with inferior efficacy outcomes.

Keywords

Adult, Humans, Receptors, Chimeric Antigen, Lymphoma, Mantle-Cell, Bendamustine Hydrochloride, Neoplasm Recurrence, Local, Immunotherapy, Adoptive, Lymphoma, Large B-Cell, Diffuse, Antigens, CD19

DOI

10.1200/JCO.22.01797

PMID

36753699

PMCID

PMC10489553

PubMedCentral® Posted Date

2-8-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes