Results of second‐line therapy in adult Philadelphia chromosome‐positive acute lymphoblastic leukemia

Background The approval of the BCR::ABL tyrosine kinase inhibitors (TKIs) and blinatumomab have improved outcomes in Ph‐positive B‐acute lymphoblastic leukemia (ALL). However, patients still relapse, and their outcomes in the TKI era have yet to be defined. Methods Patients with relapsed/primary refractory Philadelphia chromosome (pH)‐positive B‐ALL ≥16 years old treated in first salvage from 1992 to 2025 were analyzed. Results A total of 165 patients (median age, 48; range, 17–78 years) were analyzed. The overall complete remission (CR) rate was 80%. By multivariate analysis, only the use of TKIs was associated with a significant benefit for achieving CR. The median overall survival (OS) was 15 months. The 3‐year OS rate was 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, three variables were independently predictive of survival: TKI‐based therapy (hazard ratio [HR], 0.10–0.49; p values all <.001 for each TKI vs. no TKI), blinatumomab‐based therapy (HR, 0.36; p = .0058), and white blood cell ≥50 × 10 9 /L (HR, 1.96; p = .0076). Conclusions This study establishes a modern expectation of outcome of Ph‐positive B‐cell ALL treated in salvage 1. Third‐generation TKI plus blinatumomab combinations should be given consideration in this setting.