Efficacy and Safety of CAR‐T Cell Therapy in Relapsed/Refractory B‐Cell Acute Lymphoblastic Leukemia With Central Nervous System Involvement

Abstract

Central nervous system (CNS) involvement in B‐cell acute lymphoblastic leukemia (B‐ALL) is associated with relapse, treatment refractoriness, and poor prognosis. Although chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable efficacy in relapsed/refractory (R/R) B‐ALL, its efficacy and safety in CNS leukemia (CNSL) remain unclear. We retrospectively analyzed 113 R/R B‐ALL patients who received CAR‐T cell therapy, stratifying them into CNS‐positive (n = 22) and CNS‐negative (n = 91) groups based on the presence of CNSL prior to infusion. At Day 28 after CAR‐T infusion, the overall complete remission (CR) rate was 81.8%, with no significant difference between groups. The incidence of cytokine release syndrome (CRS) and neurotoxicity was comparable. The 3‐year cumulative incidence of relapse (CIR), event‐free survival (EFS), and overall survival (OS) were similar between groups. However, CNSL patients exhibit a higher cumulative relapse rate following CAR‐T‐induced remission, with an increased risk of CNS relapse compared to patients without CNS involvement. Multivariate analysis identified allo‐HSCT as consolidation post‐CAR‐T as an independent protective factor for improved EFS and OS in CNSL patients. In conclusion, CAR‐T therapy offers similar efficacy and safety in R/R B‐ALL patients regardless of CNS involvement. Furthermore, CAR‐T cell therapy was not sufficient to maintain sustained remission, and consolidative allo‐HSCT may improve long‐term survival in this high‐risk group.