Comparative efficacy and long-term survival of CD19/22 versus CD19 CAR-T immunotherapy in Relapsed/Refractory B-ALL with TP53 alterations.
In a single-center retrospective comparison of 55 patients with TP53-altered relapsed/refractory B-ALL, CD19/22 CAR-T was associated with higher MRD-negative remission and better 3-year overall and leukemia-free survival than CD19 CAR-T, particularly among patients receiving subsequent allogeneic HSCT.
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In a single-center retrospective comparison of 55 patients with TP53-altered relapsed/refractory B-ALL, CD19/22 CAR-T was associated with higher MRD-negative remission and better 3-year overall and leukemia-free survival than CD19 CAR-T, particularly among patients receiving subsequent allogeneic HSCT.
Research significance
The reported clinical associations support the hypothesis that dual CD19/22 targeting, potentially followed by allogeneic HSCT, may improve disease control in TP53-altered relapsed/refractory B-ALL; however, superiority and causality remain unproven because the comparison was small, retrospective, single-center, and apparently nonrandomized.
Source abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: A single-center retrospective clinical study.