SPOTLIGHT: Ponatinib in Ph+ ALL and MRD Negativity

Findings from the PhALLCON study (NCT03589326) presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting showed that ponatinib (Inclusig; Takeda) had higher rates of minimal residual disease (MRD) negativity compared with imatinib mesylate (Gleevec; Novartis), which correlates with better long-term survival in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL), explained Ibrahim Aldoss, MD, an associate professor in the Division of Leukemia, Department of Hematology and Hematopoietic Cell Transplantation at City of Hope in Duarte, California, in an interview with The American Journal of Managed Care (AJMC).

AJMC: What do the event-free survival results look like for PhALLCON?

Ibrahim Aldoss, MD | Image: ASCO

Aldoss: We don’t have long-term follow-up yet on the PhALLCON study, and we’re waiting for the data to be mature to show [whether] ponatinib is truly associated with improved event-free survival compared with imatinib. Now it depends what you call events. In the PhALLCON study, even with the shorter follow-up, we were able to see that PFS, progression-free survival, has improved with ponatinib compared [with] imatinib. When you account for patients who don’t achieve MRD negativity, or they relapse with MRD, where usually most of us will intervene at that level [is] before the patient has fully relapsed disease.

What I’m presenting at ASCO [is] for patients who didn’t achieve MRD negativity after 3 months because we expect these patients don’t do as well as someone who achieves MRD negativity at 3 months; we actually are able to see that event-free survival was better for patients who continue receiving ponatinib compared [with] imatinib in this post hoc analysis.

AJMC: What additional insights into the use of MRD as an end point have we gained from PhALLCON?

Aldoss: For patients achieving MRD negativity, it seems that outcomes [improve]; long-term survival and event-free survival outcomes. Again, we’re still waiting for a longer follow-up [for] more insight about the benefit of early MRD negativity from PhALLCON, but we have seen this benefit actually [in] another study for patients who achieve early complete molecular remission with Ph+ ALL.

AJMC: What is the adverse event profile in long-term maintenance
with ponatinib?

Aldoss: We haven’t seen any difference in treatment-emergent adverse events between the 2 cohorts, even [though] they continue therapy beyond induction, so they have longer exposure to TKIs [tyrosine kinase inhibitors]. And even for the arterial events, occlusive events, they were rare...in both imatinib and ponatinib arms, and they were comparable. They were not different between both. And we attribute this to the dose of ponatinib that was used in the PhALLCON study, where we start with 30 mg, and for patients who achieve complete molecular remission, the dose was dropped to 15 mg. But also the eligibility criteria of the PhALLCON study excluded patients with severe cardiovascular comorbidities that put them at risk with exposure to some TKIs.

This transcript was lightly edited.

Reference
Aldoss I, Vachhani P, Kantarjian HM, et al. MRD negativity after end of induction in the phase 3 PhALLCON trial: a post hoc analysis. J Clin Oncol. 2025;43(suppl 16):6510. doi:10.1200/JCO.2025.43.16_suppl.6510