CAR T-cell therapy in patients with acute lymphoblastic leukemia: a systematic review and meta-analysis

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape of relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (B-ALL), with high remission rates across various CAR T-cell constructs. However, the durability of these responses remains a major challenge, with many patients experiencing relapse after an initial remission. This systematic review and meta-analysis aimed to compare the efficacy and safety of different CAR T-cell constructs across 40 clinical trials, including a total of 1540 R/R B-ALL patients. We assessed the impact of patient demographics, prior treatment exposure, and construct characteristics on treatment outcomes. The pooled complete remission rate (CRR) was 83.4% (I² = 49%), with a minimal residual disease-negative complete remission (MRDneg-CR/CRi) rate of 92.7% (I² = 48%). 4-1BB co-stimulatory domain constructs showed higher MRDneg-CR/CRi rates compared with CD28 (94.0% vs. 84.4%p = 0.048) and a lower incidence of immune effector cell-associated neurotoxicity syndrome. Additionally, CAR T-cell products targeting CD19 or CD19/CD22 patients presented higher MRDneg-CR/CRi rates than those targeting CD22 alone. In conclusion, our findings suggest that 4-1BB-based CAR T-cell therapy targeting CD19 offers the best efficacy and safety profile in R/R B-ALL.