CD19 特异性 CAR-T 细胞疗法在伴中枢神经系统白血病的 B 细胞急性淋巴细胞白血病患者中的疗效与安全性

Few studies have described chimeric antigen receptor (CAR) T-cell therapy for patients with B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system leukemia (CNSL) because of concerns regarding poor response and treatment-related neurotoxicity.

Our study included 48 patients with relapsed/refractory B-ALL with CNSL to evaluate the efficacy and safety of CD19-specific CAR T cell-based therapy. The infusion resulted in an overall response rate of 87. 5% (95% confidence interval [CI], 75. 3-94. 1) in bone marrow (BM) disease and remission rate of 85. 4% (95% CI, 72. 8-92. 8) in CNSL. With a median follow-up of 11. 5 months (range, 1. 3-33. 3), the median event-free survival was 8. 7 months (95% CI, 3. 7-18. 8), and the median overall survival was 16.

0 months (95% CI, 13. 5-20. 1). The cumulative incidences of relapse in BM and CNS diseases were 31. 1% and 11. 3%, respectively, at 12 months (P = . 040). The treatment was generally well tolerated, with 9 patients (18. 8%) experiencing grade 3 cytokine release syndrome. Grade 3 to 4 neurotoxic events, which developed in 11 patients (22. 9%), were associated with a higher preinfusion disease burden in CNS and were effectively controlled under intensive management.

Our results suggest that CD19-specific CAR T cell-based therapy can induce similar high response rates in both BM and CNS diseases. The duration of remission in CNSL was longer than that in BM disease. CD19 CAR T-cell therapy may provide a potential treatment option for previously excluded patients with CNSL, with manageable neurotoxicity. The clinical trials were registered at www. clinicaltrials. gov as #NCT02782351 and www. chictr. org. cn as #ChiCTR-OPN-16008526.