Multicenter phase 2 trial of bicistronic CD19/CD22 CAR T-cell therapy in pediatric B-cell acute lymphoblastic leukemia

CD19-directed CAR T-cll therapy induces high remission rates in relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), but relapse, often due to antigen loss, remains a major challenge. Dual-targeting CD19/CD22 CAR T-cell strategies may be associated with reduced antigen-negative relapse and improved remission durability. A phase 2 trial at 5 centers in China evaluated bicistronic CD19/CD22 CAR T-cell therapy in pediatric patients with R/R B-ALL. Among 261 patients (37.6% female; mean age 8.2 years; SD 3.8), 259 (99.2%) achieved complete remission with negative minimal residual disease. Event-free survival (EFS) was 70.9% (95% CI 65.6-76.7) at 12 months, 63.2% (57.6-65.0) at 24 months, and 61.7% (55.9-68.0) at 36 months. Consolidative transplant was associated with improved EFS; at 24 months the EFS was 57.9% (95% CI 51.6-65.0) in patients without a transplant versus 85.7% (76.5-96.1) in patients with a transplant (p=0.004). Grade 3 to 4 cytokine release syndrome occurred in 49.4% and immune effector cell-associated neurotoxic effects occurred in 13.0%, but mortality was low.The authors conclude that these results suggest that bicistronic CD19/CD22 CAR T-cell therapy was associated with high rates of deep remission and durable disease control in pediatric R/R B-ALL.