Ponatinib Shows promise in ​Ph+ ALL Treatment, Achieving MRD Negativity

‍ Updated June 1, 2025
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Patients with newly diagnosed ​Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)⁢ who‌ don’t initially‌ respond to the tyrosine kinase inhibitor (TKI) ponatinib can still⁣ achieve minimal residual disease (MRD) ‌negativity,‌ according to research⁣ presented at the 2025 American Society‍ of ⁤Clinical Oncology (ASCO) Annual Meeting.

The‌ study, a post-hoc ⁣analysis of the PhALLCON trial, suggests that continuing ponatinib treatment beyond ⁣the ‍initial cycles can lead to improved outcomes, ‌even in patients who don’t achieve⁢ MRD negativity early on.Ph+ ALL, once‍ a challenging subtype of adult ALL, has seen improved ​outcomes‌ with TKIs.

Ibrahim Aldoss, MD, of City of Hope hospital, said the findings support the⁢ clinical benefit and tolerability of continuing ponatinib beyond the ⁣standard induction cycles for patients with Ph+​ ALL ‍who have not⁣ achieved ⁢MRD negativity.

The PhALLCON trial compared ‍ponatinib to imatinib, an​ earlier-generation TKI. Ponatinib demonstrated a significantly higher rate of‍ MRD-negative complete response by the end of cycle 3 compared to imatinib (34.4% vs. 16.7%).

Researchers then analyzed 113 patients who continued treatment ⁣after induction. ⁣of these, 48% in the ponatinib group and 33% in the imatinib group achieved MRD negativity after induction cycle 4.

event-free survival was longer in the⁤ ponatinib group among patients who‍ did not achieve MRD negativity by the end of induction.The two-year event-free survival‌ rates were 82% with ponatinib and 62% with imatinib.

While ponatinib has⁤ been linked⁤ to ⁣vascular toxicity at higher doses, ⁣these events were rare ​in the ‌study, likely due to the lower dose of 30 mg/day used in the PhALLCON trial,⁢ which⁢ was further reduced to 15 mg/day after induction.

Aldoss⁢ noted the ⁢benefits extended ‍to older ‌patients, suggesting that the stringent criteria ⁢used in​ the trial for⁣ excluding patients with cardiovascular disease should be considered in patient⁣ selection.

“We ⁣feel that using a‌ more optimized, safer lower dose was actually​ the reason ⁢why we’re seeing comparable⁣ safety and lower‍ arterial occlusive events ⁣in this study,” Aldoss said.

What’s next

Researchers suggest that MRD negativity‍ is an important indicator of long-term survival in Ph+ ALL. The​ findings indicate⁢ that ponatinib may offer a valuable treatment option, even when MRD negativity ​is delayed.