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 - 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.
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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 -