复发/难治性婴儿 ALL 研究性 CAR-T 细胞治疗后的可行性与良好缓解

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.