Second-line therapy outcomes in Ph+ ALL: A retrospective analysis

Results from a retrospective analysis of second-line therapy outcomes in 165 patients with relapsed/refractory (R/R) Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) treated in first salvage at the MD Anderson Cancer Center between 1992 and 2025 were published in Cancer by Kantarjian et al. Outcomes included response rates and survival.

Key data: The overall complete remission (CR) rate was 80%. Salvage therapy with imatinib (odds ratio [OR], 37.7; p = 0.0003), second-generation tyrosine kinase inhibitors (TKIs; OR, 30.9; p < 0.0001), and third-generation TKIs (OR, 25.7; p < 0.0001) were associated with higher CR rates vs no TKI. Prior allogeneic hematopoietic stem cell transplantation (allo-HSCT) was an independent predictor of a lower CR rate on multivariate analysis (OR, 0.21; p = 0.0188). The median overall survival (OS) was 15 months, with a 3-year OS rate of 31%. The 3-year OS rate was 57% with third-generation TKI combinations, 38% with second-generation TKI combinations, 8% with imatinib combinations, and 0% without TKIs. By multivariate analysis, imatinib (hazard ratio [HR], 0.49; p = 0.0457), second-generation TKI (HR, 0.29; p < 0.0001), ponatinib (HR, 0.20; p < 0.0001), blinatumomab-based therapy (HR, 0.36; p = 0.0058), and white blood cell count (WBC) ≥50 × 10⁹/L (HR, 1.96; p = 0.0076) were independently predictive of survival.

Key learning: The incorporation of TKIs, particularly third-generation TKI combinations, into clinical practice has enabled substantially improved outcomes in first salvage Ph+ ALL, supporting the use of modern combination therapies in this population.