CNS relapse is still a common cause of treatment failure in R/R B-ALL, although chemotherapy, cranial irradiation, and allo-HSCT are all modalities that can be incorporated into the management of CNSL. In the present study, published on Blood by a team of Xuzhou Medical University, was reported the efficacy, toxicity, and clinical feasibility of CD19-specific CAR T cell–based therapy in patients with R/R B-ALL with CNSL. This study is the first to include children and adults with CNS-3 status on a relatively large scale in a clinical trial of CAR T-cell treatment.

Robust responses were achieved in this study. An overall response rate of 87.5% for BM disease and remission rate of 85.4% for CNSL were observed, which were similar to those previously reported in pivotal CD19-specific CAR T-cell therapy trials, with overall response rates published as 81% to 93%. However, it is worth noting that all patients included in this study had CNS disease of CNS-3 status before screening, and 62.5% of patients remained in CNS-3 status after bridging therapy and before CAR T-cell infusion. Most patients had CNS involvement in the multiple-relapse setting, particularly after radiotherapy (10.4%) and allo-HSCT (20.8%), which is challenging to treat and generally leads to poor prognosis.

The above analysis suggests that CD19-specific CAR T cell–based therapy can induce high response in patients with R/R B-ALL with CNS involvement. The study suggests that CD19-specific CAR T cell–based therapy can induce similar high response rates 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 CNSL with otherwise poor prognosis.
“Considering these promising results, prospective studies featuring a larger cohort of patients with high-burden CNSLare warranted to optimize this strategy for the treatment of R/R B-ALL with CNSL.” is the comment of Authors.