Ponatinib vs Imatinib with Reduced-Intensity Chemotherapy in Patients with Newly Diagnosed Philadelphia Chromosome–Positive (Ph+) ALL: PhALLCON Study

Therapies for adults with newly diagnosed Ph+ ALL are limited and associated with poor outcomes. Ponatinib is active against native BCR-ABL1 and all identified single resistance mutations, including T315I. In the PACE study, ponatinib had 41% major hematologic response rate in heavily pretreated Ph+ ALL, but responses were not durable due to compound mutations. Ponatinib resistance in Ph+ ALL is acquired through compound mutations. Decreased likelihood of compound mutations with first-line ponatinib in Ph+ ALL may lead to more durable responses compared with ponatinib in later lines of therapy. A phase 2 study of ponatinib with chemotherapy in newly diagnosed Ph+ ALL reported improved long-term outcomes vs first/second-generation TKIs.