Multinational phase 3 trial of frontline ponatinib versus imatinib for Philadelphia chromosome-positive acute lymphoblastic leukemia

In newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (ND Ph+ALL) disease progression due to acquired resistance to first- or second-generation BCR::ABL1 TKIs is common. Ponatinib is a third-generation TKI. The multinational phase 3 PhALLCON trial compared frontline ponatinib plus reduced-intensity chemotherapy (RIC) versus imatinib (first-generation) plus RIC for ND Ph+ALL; after 20 cycles followed by ponatinib versus imatinib monotherapy. In this randomized clinical trial, ponatinib demonstrated a significantly higher minimal disease-negative complete remission rate at the end of induction (34.4% versus 16.7% with imatinib), and a comparable safety profile versus imatinib when combined with RIC. The authors conclude that these efficacy and safety results support consideration of ponatinib as a frontline TKI in combination with chemotherapy for adults with ND Ph+ALL (visual abstract).