TY - JOUR
T1 - Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma
T2 - the phase 2 ZUMA-12 trial
AU - Neelapu, Sattva S.
AU - Dickinson, Michael
AU - Munoz, Javier
AU - Ulrickson, Matthew L.
AU - Thieblemont, Catherine
AU - Oluwole, Olalekan O.
AU - Herrera, Alex F.
AU - Ujjani, Chaitra S.
AU - Lin, Yi
AU - Riedell, Peter A.
AU - Kekre, Natasha
AU - de Vos, Sven
AU - Lui, Christine
AU - Milletti, Francesca
AU - Dong, Jinghui
AU - Xu, Hairong
AU - Chavez, Julio C.
N1 - Funding Information:
The authors declare the following competing interests: S.S.N., consulting fees or honorarium from Kite, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics, Bluebird Bio, Medscape, Aptitude Health, Bio Ascend and MJH Life Sciences; personal fees from Kite, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr and Unum Therapeutics; grants, contracts or research funding from Kite, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio; and intellectual property from Takeda Pharmaceuticals and related to cell therapy. M.D., honoraria from Roche, Gilead, MSD and Novartis; consultancy or advisory role for Roche, Gilead, MSD and Novartis; speakers’ bureau participation for Roche, Gilead, MSD and Novartis; and research funding from Novartis and Roche. J.M., honoraria from Targeted Oncology, OncView, Curio, Kyowa Kirin, Physicians’ Education Resource and Seagen; consultancy or advisory role for Pharmacyclics/AbbVie, Bayer, Kite, Pfizer, Janssen, Juno/Celgene, Bristol Myers Squibb, Kyowa Kirin, Alexion, Fosun Kite, Innovent, Seagen, BeiGene, Debiopharm, Epizyme, Karyopharm, ADC Therapeutics, Servier and Genmab; speakers’ bureau participation for Kite, Kyowa, Bayer, Pharmacyclics/Janssen, Seagen, Acrotech/Aurobindo, Beigene, Verastem, AstraZeneca, Celgene/Bristol Myers Squibb and Genentech/Roche; and research funding (payed to institution) from Bayer, Gilead/Kite, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seagen, Janssen and Millennium. M.L.U., Advisory Board of Gilead and Stemline. C.T., honoraria from Bristol Myers Squibb/Celgene, AbbVie, Takeda, Novartis, Roche, Kite, and Incyte; consultancy or advisory role for Bristol Myers Squibb/Celgene, AbbVie, Takeda, Roche, Novartis, Kite, and Incyte; and travel support from Bristol Myers Squibb/Celgene, Takeda, Roche, Novartis, and Kite. O.O.O., consultancy or advisory role for Kite, Janssen, Pfizer, Novartis and Curio Science; honoraria and research funding from Kite. A.F.H., consultancy or advisory role for Bristol Meyers Squibb, Merck, Genentech, Seagen, AstraZeneca, Karyopharm, ADC Therapeutics, Takeda and Tubulis; and research funding from Bristol Myers Squibb, Merck, Genentech, Seagen, Kite, Gilead Sciences, AstraZeneca, Karyopharm and ADC Therapeutics. C.S.U., consultancy or advisory role for Atara and Kite; research funding and travel expenses from Kite. Y.L., consultancy or advisory role for Kite, Janssen, Novartis, Celgene, Bluebird Bio, Juno, Legend, Sorrento, Gamida Cell and Vineti; and research funding from Kite, Janssen, Celgene, Bluebird Bio, Merck and Takeda. P.A.R., honoraria from Novartis; consultancy or advisory role for Novartis, Celgene/Bristol Myers Squibb, Takeda, BeiGene and Karyopharm Therapeutics; speakers’ bureau participation for Kite; and research funding from Kite, Celgene/Bristol Myers Squibb, Novartis, Calibr, Xencor, MorphoSys and Tessa Therapeutics. N.K., consulting or advisory role and honoraria from Gilead, Novartis and Celgene. S.d.V., participation on a Data Safety Advisory Board for BeiGene. C.L., employment with and travel support from Kite; stock or other ownership in Gilead Sciences. F.M., employment with Kite; and stock or other ownership in Gilead. J.D., employment with Kite; stock or other ownership in Gilead Sciences; consultancy or advisory role for and intellectual property from GliaCure/Tufts. H.X., employment with Kite. J.C.C., consultancy fees for Kite, AbbVie, Janssen, ADC Therapeutics, Karyopharm, Kymera, GenMab and Novartis; speakers’ bureau participation for Morphosys, Epyzime, Bristol Myers Squibb, BeiGene and AstraZeneca; and research funding from AstraZeneca, Merck, ADC Therapeutics and Adaptive.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/4
Y1 - 2022/4
N2 - High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study (ClinicalTrials.gov NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in 40 patients with high-risk LBCL. This trial has completed accrual. The primary outcome was complete response rate (CRR). Secondary outcomes were objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), assessment of safety, central nervous system (CNS) relapse and blood levels of CAR T cells and cytokines. The primary endpoint in efficacy-evaluable patients (n = 37) was met, with 78% CRR (95% confidence interval (CI), 62–90) and 89% ORR (95% CI, 75–97). As of 17 May 2021 (median follow-up, 15.9 months), 73% of patients remained in objective response; median DOR, EFS and PFS were not reached. Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in three patients (8%) and nine patients (23%), respectively. There were no treatment-related grade 5 events. Robust CAR T-cell expansion occurred in all patients with a median time to peak of 8 days. We conclude that axi-cel is highly effective as part of first-line therapy for high-risk LBCL, with a manageable safety profile.
AB - High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study (ClinicalTrials.gov NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in 40 patients with high-risk LBCL. This trial has completed accrual. The primary outcome was complete response rate (CRR). Secondary outcomes were objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), assessment of safety, central nervous system (CNS) relapse and blood levels of CAR T cells and cytokines. The primary endpoint in efficacy-evaluable patients (n = 37) was met, with 78% CRR (95% confidence interval (CI), 62–90) and 89% ORR (95% CI, 75–97). As of 17 May 2021 (median follow-up, 15.9 months), 73% of patients remained in objective response; median DOR, EFS and PFS were not reached. Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in three patients (8%) and nine patients (23%), respectively. There were no treatment-related grade 5 events. Robust CAR T-cell expansion occurred in all patients with a median time to peak of 8 days. We conclude that axi-cel is highly effective as part of first-line therapy for high-risk LBCL, with a manageable safety profile.
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UR - http://www.scopus.com/inward/citedby.url?scp=85126747248&partnerID=8YFLogxK
U2 - 10.1038/s41591-022-01731-4
DO - 10.1038/s41591-022-01731-4
M3 - Article
C2 - 35314842
AN - SCOPUS:85126747248
SN - 1078-8956
VL - 28
SP - 735
EP - 742
JO - Nature Medicine
JF - Nature Medicine
IS - 4
ER -