Obecabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia

作者：Claire Roddie, Karamjeet Sandhu, Eleni Tholouli, Aaron C. Logan, Paul J. Shaughnessy, Pere Barba, Armin Ghobadi, Manuel Guerreiro, Deborah Yallop, Mehrdad Abedi, Jeremy Mark Pantin, Jean A. Yared, Amer Beitinjaneh, Sridhar Chaganti, Katharine A. Hodby, Tobias Menne, Martha Lucia Arellano, Ram K. Malladi, Bijal Dinesh Shah, Luke J. Mountjoy, Kristen Marie O’Dwyer, Karl S. Peggs, Pierre Lao‐Sirieix, Yiyun Zhang, Wolfram Brugger, Edgar Braendle, Martin Pulé, Michael Russell Bishop, Daniel J. DeAngelo, Jae H. Park, Elias Jabbour · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2406526 · 被引用次数：236 · 研究领域：CAR-T cell therapy research、Acute Lymphoblastic Leukemia research、Immunotherapy and Immune Responses

BACKGROUND: Obecabtagene autoleucel (obe-cel) is an autologous 41BB-ζ anti-CD19 chimeric antigen receptor (CAR) T-cell therapy which uses an intermediate-affinity CAR to reduce toxic effects and improve persistence. METHODS: We conducted a phase 1b-2 multicenter study of obe-cel in adults (≥18 years of age) with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). The main cohort, cohort 2A, included patients with morphologic disease; patients in cohort 2B had measurable residual disease. The primary end point was overall remission (complete remission or complete remission with incomplete hematologic recovery) in cohort 2A. Secondary end points included event-free survival, overall survival, and safety. RESULTS: Of the 153 enrolled patients, 127 (83.0%) received at least one infusion of obe-cel and were evaluable. In cohort 2A (94 patients; median follow-up, 20.3 months), overall remission occurred in 77% (95% confidence interval [CI], 67 to 85), with complete remission in 55% (95% CI, 45 to 66) and complete remission with incomplete hematologic recovery in 21% (95% CI, 14 to 31). The prespecified null hypotheses of overall remission (≤40%) and complete remission (≤20%) were rejected (P<0.001). In the 127 patients who received at least one obe-cel infusion (median follow-up, 21.5 months), the median event-free survival was 11.9 months (95% CI, 8.0 to 22.1); estimated 6- and 12-month event-free survival was 65.4% and 49.5%, respectively. The median overall surviva...