Ponatinib vs imatinib in patients with newly diagnosed Ph+ ALL: Results from the PhALLCON trial

Findings from the phase III PhALLCON trial (NCT03589326) were recently published in JAMA by Jabbour et al.¹ Adult patients with newly diagnosed (ND) Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) were randomized 2:1 to receive either ponatinib or imatinib with reduced-intensity chemotherapy.¹ Results from this trial led to the approval of ponatinib plus chemotherapy for adult patients with ND Ph+ ALL by the U.S. Food and Drug Administration (FDA).

The primary endpoint was met: ponatinib significantly improved the minimal residual disease (MRD)-negative complete remission (CR) rate vs imatinib (34.4% vs 16.7%; p = 0.002).

Although the study did not reach the prespecified number of events for final event-free survival (EFS) analysis at the time of this interim analysis, median EFS was notably longer with ponatinib compared with imatinib (not reached vs 29.0 months).

The safety profiles of ponatinib and imatinib were comparable, with similar rates of adverse events and arterial occlusive events, indicating ponatinib’s enhanced efficacy does not come with increased severe side effects.

These findings support the use of ponatinib as a first-line therapy in combination with chemotherapy for adult patients with newly diagnosed Ph+ ALL.