Dr Jabbour on the Significance of the FDA Approval of Ponatinib Plus Chemo for PH+ ALL

Elias Jabbour, MD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the significance of the FDA approval of ponatinib (Iclusig) in combination with chemotherapy for the frontline treatment of adult patients with newly diagnosed, Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL).

On March 19th, 2024, the FDA granted accelerated approval to ponatinib plus chemotherapy for the treatment of patients in this population based on findings from the phase 3 PhALLCON study (NCT03589326). In the randomized, active-controlled, multicenter, open-label study, the minimal residual disease (MRD)–negative complete remission (CR) rate in evaluable patients treated with ponatinib (n = 154) was 30% at the end of induction vs 12% in evaluable patients treated with imatinib (Gleevec) plus chemotherapy (n = 78). This translated to a risk difference of 0.18 (95% CI, 0.08-0.28; P = .0004). Moreover, 79% of evaluable patients in the ponatinib arm achieved a CR at the end of induction treatment compared with 63% of those in the imatinib arm.

Regarding safety, 71% percent of patients in the ponatinib arm required dose interruptions or reductions due to adverse effects (AEs), and 63% of patients experienced serious AEs. Notably, 13% of patients experienced AEs leading to permanent treatment discontinuation.

Furthermore, ponatinib's superior efficacy was obtained without additional toxicities, Jabbour says, adding that there was no difference in AEs and discontinuation between the 2 therapeutic arms. This shows that ponatinib is capable of enhancing the efficacy of chemotherapy without increased risk, Jabbour summarizes. He notes that the PhALLCON trial was also unique for using MRD-negative CR at the end of induction at 12 weeks as the primary end point. This unique end point was chosen based on data showing that patients with MRD negativity can achieve improved survival outcomes, according to Jabbour. Overall, the approval of ponatinib marks the first time a TKI has gained FDA approval in the frontline setting for patients with ALL, thereby signifying a shift in the standard of care, Jabbour concludes.