Efficacy and safety of CD19-specific CAR T-cell-based therapy in B-cell acute lymphoblastic leukemia patients with CNSL

• Neurotoxicity of CD19 CAR T-cell therapy was acceptable in R/R B-ALL with CNSL.

• CD19-specific CAR T cells could induce similar high response rate in both BM and CNS diseases.

Few studies have described chimeric antigen receptor (CAR) T-cell therapy for B-cell acute lymphoblastic leukemia (B-ALL) patients with central nervous system leukemia (CNSL) due to concerns for poor response and treatment-related neurotoxicity. Our study included 48 relapsed/refractory B-ALL (R/R B-ALL) patients with CNSL to evaluate the efficacy and safety of CD19-specific CAR T-cell-based therapy. The infusion resulted in overall response rate of 87.5% (95% confidence interval , 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 (EFS) was 8.7 months (95% CI, 3.7-18.8), and the median overall survival (OS) was 16.0 months (95% CI, 13.5-20.1). The cumulative incidences of relapse (CIR) in BM and CNS diseases were 31.1% and 11.3%, respectively, at 12 months (p=0.040). The treatment was generally well tolerated with 9 patients (18.8%) experiencing grade ≥3 cytokine release syndrome. Grade 3-4 neurotoxic events (NEs), which developed in 11 patients (22.9%), were associated with a higher pre-infusion disease burden in CNS and were effectively controlled under intensive management. Our results suggested that CD19-specific CAR T-cell-based therapy could induce similar high response rate 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 those previously excluded CNSL patients with manageable neurotoxicity. Clinical trials were registered at www.clinicaltrials.gov as # NCT02782351 and www.chictr.org.cn as # ChiCTR-OPN-16008526.