A Remodeled CAR for B-Cell Acute Lymphoblastic Leukemia

Anti-CD19 chimeric antigen receptor (CAR) T-cell agents are an established treatment for relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). Investigators report an industry-sponsored, multinational, phase 1b–2 trial of a novel CAR T-cell therapy containing a modified anti-CD19 binding domain designed to decrease cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity (ICANS) and to enhance CAR T-cell engraftment and persistence. Adults with R/R B-ALL received a split dose of obecabtagene autoleucel (obe-cel) infusion based on bone marrow tumor cell burden prior to the administration of lymphodepleting chemotherapy.

Of 153 patients, 146 (95%) had successful CAR T-cell manufacture and 127 received obe-cel infusions; 18 patients died or had progressive disease before treatment. Over 90% of patients received pre–CAR T-cell bridging chemotherapy. Among the findings:

• Of 94 patients with morphologically evident residual ALL, 55% achieved complete remission (CR), and another 21% had CR with incomplete hematologic recovery.
• Among 127 patients who received at least one obe-cel infusion, at a median follow-up of 21.5 months, estimated 6-month and 12-month event-free survival was 65.4% and 49.5%, respectively.
• Grade 3 or higher CRS occurred in 2.4% of patients; grade 3 or higher ICANS occurred in 7.1%.