Feasibility and favorable responses after investigational CAR T-cell therapy for relapsed and refractory infant ALL

Infants with B-cell acute lymphoblastic leukemia (B-ALL) continue to have significantly worse outcomes compared with older children with B-ALL, and those with relapsed or refractory (R/R) infant ALL have especially dismal outcomes with conventional treatment. CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable success in the treatment of R/R childhood B-ALL, although the majority of reports have been in noninfant patients. Barriers to the successful implementation of CAR T-cell therapy in infant B-ALL include challenges related to apheresis, product manufacturing, and disease-specific considerations such as lineage switch. We describe our experience using 2 experimental CD19 CAR T-cell products, SCRI-CAR19 or SCRI-CAR19x22, for 19 patients with R/R infant B-ALL enrolled in 3 clinical trials. CAR T-cell products were successfully manufactured in 18 of 19 (94.7%) patients, with a median age of 22.5 months at enrollment (range, 14.5-40.1). Of 17 (94.1%) treated patients, 16 achieved a complete remission without detectable minimal residual disease. The 1-year leukemia-free survival was 75%, and 1-year overall survival was 76.5%, with a median follow-up time of 35.8 months (range, 1.7-83.6). Cytokine release syndrome (CRS) occurred in 14 of 17 (82.4%) patients, with only 1 patient experiencing grade 3 CRS. Neurotoxicity occurred in 2 of 17 (11.8%) patients with all events grade ≤2. With the successful early clinical experience of CAR T-cell therapy in this population, more systematic evaluation specific to infant ALL is warranted.