Predictors of complete molecular response and impact of allo-HSCT in Ph+ ALL

Results from a retrospective, multicenter study from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND), evaluating predictors of complete molecular response (CMR) and the impact of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL; N = 467), were published in Leukemia & Lymphoma by Mohty et al. Achievement of CMR at 3 months after initiating therapy was selected as the primary molecular response endpoint, with analyses evaluating predictors of CMR and associations between CMR, allo-HSCT, relapse-free survival (RFS), and overall survival (OS).

Key data: CMR was achieved in 63.7% of patients at 3 months. In multivariate analysis, white blood cell (WBC) count >70,000/L at diagnosis (odds ratio [OR], 0.544; 95% confidence interval [CI], 0.331–0.895; p = 0.017), p210 fusion protein (OR, 0.266; 95% CI, 0.168–0.423; p < 0.001), and monosomy 7 (OR, 0.389; 95% CI, 0.196–0.774; p = 0.007) independently predicted lower odds of achieving CMR, while use of ponatinib/dasatinib (OR, 2.144; 95% CI, 1.221–3.764; p = 0.008) and intensive chemotherapy (IC) (OR, 1.828; 95% CI, 1.161–2.879; p = 0.009) predicted higher odds of achieving CMR. Among patients achieving CMR at 3 months, allo-HSCT vs no allo-HSCT improved median RFS (123.1 vs 30.3 months; p < 0.0001) but not median OS (129.2 vs 149.3 months; p = 0.07).

Key learning: These real-world results highlight the role of baseline disease features, IC, and tyrosine kinase inhibitor (TKI) selection in achieving early CMR in Ph+ ALL. Allo-HSCT may be deferred in selected patients achieving early CMR, pending prospective validation.