Review of pediatric B-ALL CAR-T therapy identifies RAS mutation outcome predictor

This is a narrative review synthesizing observational data from a cohort of 86 pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia who received CD19 CAR-T cell therapy (tisagenlecleucel). The review's scope is to identify molecular and clinical predictors of response and survival after this therapy.

The authors report that 77 of 86 patients (89.5%) achieved a complete response (CR). A key synthesized finding is that lower CR rates were associated with pre-infusion bone marrow blasts ≥20% (53.8% vs 95.9%, p<0.0001). Significantly reduced overall survival (OS) and leukemia-free survival (LFS) were also associated with bone marrow blasts ≥20% (p<0.0001 for both). Inferior OS and LFS were associated with RAS mutations (p=0.0222 and p=0.0402, respectively). A higher prevalence of RAS mutations (66% vs 37.5%) was noted in patients with CD19-negative relapses.

The authors acknowledge limitations, including that cytogenetic data were available for 84 patients, molecular profiling for 62, and survival analyses included 72 patients who received CD19 CAR-T as the sole cellular therapy. Safety data were not reported.

Practice relevance is restrained; the findings highlight RAS mutations as a key molecular predictor of outcome and suggest a potential role for risk stratification. The review does not establish causation and generalizability is limited to the pediatric population with relapsed or refractory B-ALL.