Discussant of the February ASCO Plenary session, Anjali S. Advani, MD, Staff Physician in the Department of Hematologic Oncology and Blood Disorders and Director of the Inpatient Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, noted that the PhALLCON study is the only prospective randomized trial comparing tyrosine kinase inhibitors in this patient population with chemotherapy, and she called the results “encouraging.”¹

“Ponatinib was associated with higher measurable residual disease [MRD]-negative complete remission rates and deeper, more durable responses than imatinib, with no increased rate of treatment-related emergent adverse events, such as arterial occlusive events or venous thromboembolic events,” said Dr. Advani. Despite these positive findings, however, she also noted several study limitations, including the relatively young patient population, with a low incidence of cardiovascular risk factors. “The question is whether we can generalize these results to a larger population who may be older and/or have comorbidities,” she posed. “Moreover, the study did not compare ponatinib with dasatinib, which is typically used more often in the United States.” 

Anjali S. Advani, MD

In addition, Dr. Advani noted that new treatments, such as antibody-based therapies and chimeric antigen receptor (CAR) T-cell therapies, may salvage patients who experience disease progression in the front-line setting. Dr. Advani also noted a lack of difference in overall survival between the two study arms, although follow-up is short, and the results are not yet mature, she added. Finally, Dr. Advani highlighted the changing landscape of treatment in the front-line setting, with the use of blinatumomab plus a tyrosine kinase inhibitor (either dasatinib or ponatinib). Although longer follow-up is needed, a study published by Foá et al with dasatinib plus blinatumomab demonstrated “excellent overall survival and disease-free survival, with a very low incidence of relapse,² she said.

“In conclusion, ponatinib represents an exciting treatment option, particularly for younger patients with relatively few or no cardiovascular comorbidities. However, further studies are needed to evaluate the risk/benefit of ponatinib in patients with comorbidities and to compare the efficacy of antibody-based therapies plus tyrosine kinase inhibitors with ponatinib in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia,” Dr. Advani said. 

DISCLOSURE: Dr. Advani has held a consulting or advisory role with Amgen, Beam Therapeutics, Glycomimetics, Jazz Pharmaceuticals, Kite Pharma, Kura Oncology, Nkarta, Novartis, Pfizer, Seattle Genetics, and Taiho Oncology, and has received research funding from Amgen, Glycomimetics, Immunogen, Incyte, Kite/Gilead, Macrogenics, OBI Pharma, Pfizer, Seattle Genetics, and Servier.

REFERENCES

1. Jabbour E, Kantarjian H, Aldoss I, et al: First report of PhALLCON: A phase 3 study comparing ponatinib vs imatinib in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. ASCO Plenary Series: February 2023 Session. Abstract 398868. Presented February 15, 2023.

2. Foà R, Bassan R, Vitale A, et al: Dasatinib-blinatumomab for Ph-positive acute lymphoblastic leukemia in adults. N Engl J Med 383:1613-1623, 2020.