Ponatinib in Ph+ ALL and MRD Negativity: Ibrahim Aldoss, MD

In the PhALLCON study (NCT03589326) presented at the American Society of Clinical Oncology (ASCO) meeting, ponatinib showed higher rates of minimal residual disease (MRD) negativity compared with imatinib, which correlates with better long-term survival in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL), explains Ibrahim Aldoss, MD, associate professor, City of Hope.

This transcript was lightly edited; captions were auto-generated.

Transcript

What do the long-term event-free survival results look like for PhALLCON?

We don't have long-term follow-up yet on the PhALLCON, and we're waiting for actually the data to be mature, to show if ponatinib is truly associated with improved event-free survival compared with imatinib. Now it depends how 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 to imatinib. When you count for patients who don't achieve MRD negativity, or they relapse actually with MRD, where usually, most of us will intervene at that level before the patient has fully relapsed disease. But in 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 to imatinib in this post hoc analysis.

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

For patients achieving MRD negativity, it seems that outcomes do well. Well with long-term survival and event-free survival outcomes, again. I mean, we're still waiting for a longer follow-up [for] more insight about the benefit of early MRD negative from PhALLCON, but we have seen this benefit actually [in] another study for patients who achieve early complete molecular remission with Ph+ ALL.

What is the side effect profile in long-term maintenance with ponatinib?

We haven't seen any difference in treatment-emergent adverse events between the 2 cohorts, even [though] they continue therapy beyond actually induction, so they have longer. They've [had] more exposure to TKIs [tyrosine kinase inhibitors]. And even for the arterial events, occlusive events, they were rare, actually 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.