Comparative efficacy and long-term survival of CD19/22 versus CD19 CAR-T immunotherapy in Relapsed/Refractory B-ALL with TP53 alterations

Patients with refractory/relapsed (R/R) B-cell acute lymphoblastic leukemia (B-ALL) harboring TP53 alterations have a dismal prognosis due to profound chemoresistance. While CD19 chimeric antigen receptor T-cell (CAR-T) therapy has shifted the treatment landscape, long-term efficacy in this high-risk subset remains limited. The dual-target CD19/22 CAR-T has been developed to enhance anti-tumor activity; however, its comparative efficacy and long-term survival relative to CD19 CAR-T in this high-risk population remain unclear and require further elucidation to inform clinical decision-making. This study included 55 patients with TP53-altered R/R B-ALL who were enrolled in clinical trials (NCT03919240, NCT03275493, and NCT03614858) and treated with either CD19 (n = 27) or CD19/22 (n = 28) CAR-T therapy. The outcomes assessed included the complete remission (CR) rate, minimal residual disease (MRD)-negative CR rate, overall survival (OS), leukemia-free survival (LFS), and cumulative incidence of relapse (CIR). Multivariable Cox regression models were used to estimate hazard ratios (HRs) for OS and LFS. The CR rate was high in both groups (CD19/22: 100%; CD19: 88.89%). Notably, the MRD-negative CR rate was higher with CD19/22 CAR-T therapy (75.00% vs. 29.63%, p = 0.0011), and was confirmed as an independent favorable prognostic factor. The CD19/22 CAR-T also demonstrated markedly better long-term survival, with 3-year OS (59.55% vs. 25.49%, p = 0.0050) and LFS (57.29% vs. 17.64%, p = 0.0047) rates. Among the 32 patients who underwent consolidative allo-HSCT after CAR-T, the CD19/22 CAR-T group achieved superior 3-year survival (OS: 72.34% vs. 30.77%, p = 0.0089; LFS: 76.69% vs. 23.07%, p = 0.0041) and lower CIR (23.30% vs. 75.00%, p = 0.0182). Multivariable analysis established CD19/22 CAR-T therapy and bridging to allo-HSCT as independent predictors of improved LFS. CD19/22 CAR-T immunotherapy, particularly when followed by allo-HSCT, represents a promising and clinically effective treatment paradigm for R/R B-ALL with TP53 alterations. A single-center retrospective clinical study.