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Neurotoxicity Acceptable in CD19 CAR-T Cell Therapy for B-ALL with CNS Leukemia

ALL

CD19-directed CAR T-cell therapy could induce similar high response rates in patients with B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system leukemia (CNSL), and may provide a potential treatment for this patient population, according to a recent study.

There are few treatment options for patients with CNSL that is refractory to conventional CNS-directed therapies,” wrote Yuekun Qi of The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. “CNSL has rarely been the focus of any clinical trial of CAR T-cell therapy due to concerns for poor response and treatment-related neurotoxicity.

To look at optimal CAR T-cell based therapeutic strategies for this patient population, the researchers conducted a retrospective study of CD19-specific CAR Tcell based therapy in 48 patients with relapsed/refractory B-ALL and CNSL. Patients were categorized as CNS-1 status (3 patients), CNS-2 status (15 patients), and CNS-3 status (30 patients) by the last assessment before CAR T-cell infusion. The median age of patients was 31.

The overall response rate was 87.5% in bone marrow disease and a remission rate of 85.4% in CNSL. The researchers noted that the response rate of CNSL was higher in patients receiving CNS-directed bridging treatment compared with no bridging treatment (96.3% vs. 71.4%; P=.034).

With a median follow-up of about one year, the median event-free survival was 8.7 months, and the median overall survival was 16.0 months. Patients with CNS-3 status before CAR T-cell infusion had worse median event-free survival than those with CNS-1/2 status (5.1 vs. not reached vs. 15.0 months, P=.049). There were no differences in overall survival among the three groups.

Cumulative incidences of relapse at 12 months was 31.1% in bone marrow and 11.3% in CNSL.

Grade 3, or worse cytokine release syndrome (CRS), occurred in 18.8% of patients. Grade 3-4 neurotoxic events (NEs) developed in 22.9% of patients; these were associated with a higher pre-infusion disease burden in CNS and were controlled with intensive management.

The safety analysis revealed that high-grade CRS and NEs occurred in comparable incidences as previously reported, suggesting that CAR T-cell therapy for CNSL may act as an effective therapeutic strategy without significantly increased risk of neurotoxicity,” the researchers wrote, noting though that the analysis is limited by its retrospective nature.

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. Blood.2022 Mar 28;doi: 10.1182/blood.2021013733.

 

 

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