Dr Aldoss on the Utility of Ponatinib in Ph+ ALL

Ibrahim Aldoss, MD, hematologist-oncologist, associate professor, Division of Leukemia, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope; member, the Gehr Family Center for Leukemia Research; codirector, the Hematology Tissue Bank, City of Hope and the Leukemia Registry, discusses the utility of ponatinib (Iclusig) in the phase 3 PhALLCON trial (NCT03589326) in patients with newly diagnosed, Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL).

When considering the use of the now-FDA approved ponatinib in patients with newly diagnosed, Ph-positive ALL, it's essential to assess potential adverse events (AEs) that may impact patient safety and treatment continuation, Aldoss begins. The most common AEs observed in PhALLCON were similar between patients receiving ponatinib and those receiving imatinib, according to Aldoss. Importantly, the rate of treatment discontinuation due to was approximately 12% in both treatment arms, he explains.

One significant safety concern associated with ponatinib is the risk of arterial occlusive events, including venous thromboembolism, Aldoss expands. However, the incidence of these events was comparable between the ponatinib and imatinib arms, with only a slight difference noted, Aldoss emphasizes. For instance, arterial occlusive events occurred in approximately 2.5% of patients receiving ponatinib compared with approximately 1.2% of patients receiving imatinib, Aldoss notes. Similarly, the rate of venous thromboembolism was approximately 12% in both treatment groups, highlighting a consistent risk profile across the study cohorts, he explains. The lower incidence of arterial events with ponatinib may be attributed to the modified dosing strategy employed in the trial, according to Aldoss. Unlike previous protocols that used a 45-mg starting dose of ponatinib, the study initiated ponatinib at 30 mg once daily, with a recommended reduction to 15 mg once daily for patients achieving complete molecular remission, Aldoss elucidates. Additionally, more stringent exclusion criteria based on previous cardiovascular risk factors were implemented to enhance patient safety, Aldoss says.

In summary, ponatinib has demonstrated superior efficacy vs imatinib in patients with Ph-positive ALL, indicating promising outcomes for this patient population, Aldoss explains. With continued follow-up, additional secondary end points may further elucidate ponatinib's efficacy and safety advantages, he concludes.