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

Abstract

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. Patients with relapsed/primary refractory Philadelphia chromosome (pH)-positive B-ALL ≥16 years old treated in first salvage from 1992 to 2025 were analyzed. 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 × 10⁹/L (HR, 1.96; p = .0076). 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.