CD19 CAR T-cell therapy may be a treatment option, with manageable neurotoxicity, for patients with B-cell acute lymphoblastic leukemia who have relapsed or refractory central nervous system (CNS) disease, Chinese researchers report in a retrospective analysis published in March in Blood.
At a median follow-up of 11.5 months, median event-free survival was 8.7 months and median overall survival 16 months among successively screened patients (N=48) who received isolated anti-CD19 (n=37, 77.1%) or combined anti-CD19 and anti-CD22 CAR T-cells (n=11, 22.9%). At 12 months, the cumulative incidence of relapse was 31.1% for bone marrow (BM) disease and 11.3% for CNS disease. The median duration of response was 17 months for BM disease and not reached for CNS disease.
Patients’ median age was 31 years, with more than 60% aged under 40 years; 36 patients (75%) had combined bone marrow and CNS disease and 31 (64.6%%) had poor-risk cytogenetic aberrations. Patients had received a median of 4 prior lines of therapy; 10 had relapsed following allogeneic stem cell transplantation. Nine patients (18.8%) experienced grade 3 or higher cytokine release syndrome and 11 patients (22.9%) grade 3 or higher neurotoxic events; neurotoxic events were associated with a higher pre-infusion CNS disease burden.
The findings suggest “that CD19-specific CAR T-cell-based therapy could induce [a] similar high response rate in both BM and CNS diseases, with an acceptable safety profile under intensive management. CD19-specific CAR T-cell therapy provides a potential treatment option for a cohort of previously excluded [patients with CNS leukemia] with an otherwise poor prognosis,” the authors write. They acknowledged that the study was limited by incomplete information about CAR T-cell kinetics in CNS and by the retrospective nature of the analysis.
- Qi Y, Zhao M, Hu Y, et al. Efficacy and safety of CD19-specific CAR T-cell-based therapy in B-cell acute lymphoblastic leukemia patients with CNSL [published online ahead of print, 2022 Mar 25]. Blood. 2022;blood.2021013733. doi:10.1182/blood.2021013733