Overall survival with ponatinib versus allogeneic stem cell transplantation in Philadelphia chromosome-positive leukemias with the T315I mutation.

Background: Effective treatment options for patients with chronic myeloid leukemia (CML) or Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) who have the threonine to isoleucine mutation at codon 315 (T315I) are few. The objective of this study was to compare overall survival (OS) between patients with CML and those with Ph+ ALL who received treatment with ponatinib versus allogeneic stem cell transplantation (allo-SCT).

Methods: A post hoc, retrospective, indirect comparison of OS among patients who received single-agent ponatinib in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial with those who underwent allo-SCT as reported to the European Bone Marrow Transplant registry, stratified by CML disease phase and Ph+ ALL, was conducted. Kaplan-Meier survival curves and multivariate Cox proportional-hazards models were used to compare OS between intervention groups, adjusting for time from diagnosis to intervention, age, sex, and geographic region; 24-month and 48-month OS rates and median OS were reported.

Results: After adjustment for potential confounders, 24-month and 48-month OS rates were significantly higher in patients with chronic-phase CML (CP-CML) who received ponatinib compared with those who underwent allo-SCT (24 months: 84% vs 60.5%, respectively; P = .004; 48 months: 72.7% vs 55.8%, respectively; P = .013), with a hazard ratio (HR) of 0.37 (95% confidence interval [CI], 0.16-0.84; P = .017). In patients who had accelerated-phase CML, OS rates were not significantly different between the groups (HR, 0.90; 95% CI, 0.20-4.10; P = .889). In patients who had blast-crisis CML and those with Ph+ ALL, ponatinib was associated with shorter OS compared with allo-SCT (blast-crisis CML: HR, 2.29 [95% CI, 1.08-4.82; P = .030]; Ph+ ALL: HR, 2.77 [95% CI, 0.73-10.56; P = .146]).

Conclusions: Although allo-SCT remains an important treatment option for patients with T315I-positive advanced CML and Ph+ ALL, ponatinib represents a valuable alternative for patients with T315I-positive CP-CML. Cancer 2017;123:2875-80. © 2017 American Cancer Society.