Abstract:

Objective To analyze the efficacy and safety of dual-targeted CD19/CD22 chimeric antigen receptor T-cells (CAR-T) in the treatment of refractory/relapsed B-lineage acute lymphoblastic leukemia (B-ALL) in children with MLL gene rearrangement (MLL-r). Methods The clinical data of children with MLL-r positive R/R B-ALL treated with dual-targeted CD19/CD22 CAR-T therapy between October 2019 and November 2021 were retrospectively analyzed. Results A total of 37 children (24 boys and 13 girls) with MLL-r positive R/R B-ALL were included and the median age was 1.2 (0.5-2.6) years at diagnosis, of whom 17 (45.9%) had infantile leukemia. At a median time of 9 (7-13) days after CAR-T cell infusion, 37 patients achieved a complete response rate of 100%. With a median follow-up of 28.2 (11.3 to 30.9) months, the 3-year overall survival rate was 67.6% (95% CI: 52.5 to 82.7%), and the 3-year event-free survival rate was 59.5% (95% CI: 43.6 to 75.4%).Twenty-eight patients (75.7%) underwent allogeneic hematopoietic stem cell transplantation after CAR-T cell therapy, and the median time between CAR-T infusion and transplantation was 83 (61 to 92) days. The 2-year OS for children who received consolidation grafts was 75.0% (95% CI: 58.9 to 91.1%), compared to 44.4% (95% CI 11.9 to 76.9%) for those who did not receive grafts. The difference between the two groups was not statistically significant (P=0.068). A total of 13 patients (35.1%) relapsed, and the median time from cell infusion to recurrence was 156 (86 to 202) days. Among them, 4 cases had double-positive recurrence of CD19 and CD22, 2 cases had double-negative recurrence of CD19 and CD22, 4 cases had CD19-negative recurrence, 1 case had myeloid transformation, and the other 2 cases were unclear. Cytokine release syndrome occurred in 97.3% (36/37) of patients in this study, with 29.7% (11/37) achieved grades 3 to 4. Immune effector cell-associated neurotoxicity syndrome was observed in 5 (13.5%) patients. There were no deaths due to CAR-T comorbidities.Conclusions CD19/CD22 CAR-T cell therapy is effective in inducing rapid remission in MLL-r R/R childhood B-lineage acute lymphoblastic leukemia with tolerable side effects.

Key words: chimeric antigen receptor-modified T cell, MLL rearrangement, acute lymphoblastic leukemia, refractory/relapsed, child