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

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 WangRahul Banerjee, David B. Miklos, Aaron P. Rapoport, Lazaros Lekakis, Armin Ghobadi, Sattva S. Neelapu, Yi Lin, Michael L. Wang, Michael D. Jain

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

PURPOSEBrexucabtagene 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 METHODSPatients 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.RESULTSOf 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.CONCLUSIONIn 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.

Original languageEnglish (US)
Pages (from-to)2594-2606
Number of pages13
JournalJournal of Clinical Oncology
Volume41
Issue number14
DOIs
StatePublished - May 10 2023

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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