Ponatinib Shows Promise in PhALLCON Study for Ph+ ALL Treatment

In discussing the phase 3 PhALLCON study (NCT03589326), Ibrahim Aldoss, MD, highlights the continued benefit of ponatinib (Iclusig) in treating patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL), even if the study’s primary end point was not met. He noted that patients who remained on ponatinib still had a strong likelihood of achieving measurable residual disease (MRD) negativity, which correlates with improved long-term outcomes.

Ponatinib, a third-generation tyrosine kinase inhibitor (TKI), demonstrated superior efficacy compared to imatinib (Gleevec), despite previous concerns about arterial occlusive events associated with its use. These safety concerns appear to be mitigated in the PhALLCON trial, where a reduced dosing strategy was implemented. Patients began at 30 mg daily, compared to the historical 45 mg dose, and dosing was further lowered to 15 mg once molecular remission was achieved.

Aldoss emphasizes that while early results are promising, longer-term data are still pending, as the follow-up in the current PhALLCON analysis is relatively short. Updated results will help better define the durability of responses and the long-term safety profile of ponatinib compared with imatinib.

He also acknowledged that the treatment landscape for Ph+ ALL is evolving quickly. There is a growing interest in integrating immunotherapy earlier in the treatment course. Agents such as blinatumomab (Blincyto) are now being used as backbone regimens, and novel approaches—including combining TKIs like ponatinib with CAR T-cell therapy in the frontline setting—are under investigation.

Ultimately, Aldoss underscores the importance of identifying the most potent and effective TKI options to serve as the foundation for future combination strategies aimed at improving outcomes in Ph+ ALL.