RCT: Ponatinib shows superior MRD-negative complete remission rates compared to Imatinib in newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia – JAMA

This global phase 3 randomized clinical trial investigated the efficacy and safety of ponatinib versus imatinib in adults with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). The study, conducted across 77 sites, enrolled 245 patients who were randomized in a 2:1 ratio to receive either ponatinib (30 mg/d) or imatinib (600 mg/d) alongside reduced-intensity chemotherapy. The primary endpoint of the trial was minimal residual disease–negative (MRD-negative) complete remission, assessed at the end of cycle 3. Results showed that ponatinib achieved a significantly higher MRD-negative complete remission rate of 34.4% compared to 16.7% with imatinib. Additionally, the safety profile between the two drugs was comparable, with arterial occlusive events being rare and similar across groups. These findings suggest ponatinib as a potentially preferable frontline therapy in this patient population due to its superior efficacy in achieving MRD-negative status without compromising safety.

Reference (link to abstract – $ for full-text):

Jabbour E, Kantarjian HM, Aldoss I, et al. (2024). Ponatinib vs Imatinib in Frontline Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. Published online May 9, 2024. doi:10.1001/jama.2024.4783