Dr Jabbour on the Results of the PhALLCON Trial in Newly Diagnosed Ph+ ALL

Elias Jabbour, MD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses outcomes from the phase 3 PhALLCON trial (NCT03589326) in patients with Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL).

PhALLCON evaluated chemotherapy in combination with either ponatinib (Iclusig) or imatinib (Gleevec) in patients with newly diagnosed, Ph-positive ALL. Patients received ponatinib at 30 mg daily or imatinib at 600 mg daily in combination with reduced-intensity chemotherapy through the end of induction, consolidation, and post-consolidation. Notably, patients were only allowed to continue study treatment per investigator’s discretion if they had achieved a complete response (CR) or a CR with incomplete hematologic recovery and MRD negativity at the end of induction. After cycle 20, patients received ponatinib or imatinib monotherapy until unacceptable toxicity or disease progression. The findings from this trial supported the March 2024 FDA accelerated approval of ponatinib plus chemotherapy for this indication.

PhALLCON met its primary end point of minimal residual disease (MRD)–negative CR for 4 weeks at the end of induction. Ponatinib induced an MRD-negative CR rate of 30% vs 12% with imatinib (risk difference, 0.18; 95% CI, 0.08-0.28; P = .0004). Other key end points included event-free survival (EFS) and overall survival (OS), which remained immature at the most recent data cutoff date. Notably, molecular relapse was not considered an event in PhALLCON, Jabbour says. Therefore, patients in the imatinib arm who developed MRD-positive disease were permitted to cross over to receive ponatinib. Despite the trial’s crossover design, more patients who were initially enrolled in the imatinib arm received subsequent therapy compared with those in the ponatinib arm, Jabbour explains.

Uncensored EFS outcomes trended in favor of ponatinib vs imatinib; the median EFS was not reached with ponatinib and was reached with imatinib (HR, 0.652, 95% CI, 0.385-0.455), Jabbour emphasizes. Longer follow-up is needed to determine how the EFS and OS differences between the 2 arms will mature. These data may lead to the full FDA approval of ponatinib for patients with newly diagnosed, Ph-positive ALL, Jabbour concludes.