TY - JOUR
T1 - Brexucabtagene Autoleucel for Relapsed or Refractory Mantle Cell Lymphoma in Standard-of-Care Practice
T2 - Results From the US Lymphoma CAR T Consortium
AU - Wang, Yucai
AU - Jain, Preetesh
AU - Locke, Frederick L.
AU - Maurer, Matthew J.
AU - Frank, Matthew J.
AU - Munoz, Javier L.
AU - Dahiya, Saurabh
AU - Beitinjaneh, Amer M.
AU - Jacobs, Miriam T.
AU - Mcguirk, Joseph P.
AU - Vose, Julie M.
AU - Goy, Andre
AU - Andreadis, Charalambos
AU - Hill, Brian T.
AU - Dorritie, Kathleen A.
AU - Oluwole, Olalekan O.
AU - Deol, Abhinav
AU - Paludo, Jonas
AU - Shah, Bijal
AU - Wang, Trent
AU - Banerjee, Rahul
AU - Miklos, David B.
AU - Rapoport, Aaron P.
AU - Lekakis, Lazaros
AU - Ghobadi, Armin
AU - Neelapu, Sattva S.
AU - Lin, Yi
AU - Wang, Michael L.
AU - Jain, Michael D.
N1 - Funding Information:
Dr Y. Wang would like to acknowledge the ASCO Conquer Cancer Career Development Award. Dr M.T. Jacobs would like to acknowledge K12CA167540 (Paul Calabresi K12 Career Development Award for Clinical Oncology), ASCO Conquer Cancer Young Investigator Award, and Dean's Scholars Award from the Washington University Division of Physician-Scientists (funded by the Burroughs Wellcome Fund Physician-Scientist Institution Award).
Funding Information:
NCI cancer support grant to the Moffitt Cancer Center (P30 CA076292).
Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/5/10
Y1 - 2023/5/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85159193566&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85159193566&partnerID=8YFLogxK
U2 - 10.1200/JCO.22.01797
DO - 10.1200/JCO.22.01797
M3 - Article
C2 - 36753699
AN - SCOPUS:85159193566
SN - 0732-183X
VL - 41
SP - 2594
EP - 2606
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 14
ER -