New Orleans—Ponatinib shows ”early, deep and durable” molecular responses among patients with chronic myeloid leukemia (CML) and Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) that is resistant or intolerant to dasatinib or nilotinib, or with the T315I BCR-ABL mutation, according to 2-year follow-up data from the phase 2 open-label PACE trial.

Results were presented at the 55th American Society of Hematology Annual Meeting and Exposition.

“Ponatinib has confirmed substantial activity in these heavily pretreated Ph+ [patients with] leukemia who have limited available treatment options, with a safety profile reflective of the population,” reported lead study author Jorge E. Cortes, MD, of the University of Texas M.D. Anderson Cancer Center in Houston, TX.

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The oral pan-BCR-ABL inhibitor ponatinib was delivered at 45 mg daily to 449 patients; primary end points were major cytogenic response (MCyR) within 12 months for chronic-phase CML (CP-CML), and major hematologic response (MaHR) within 6 months for advanced Ph+ leukemia.

As of September 2013, at a median follow-up of 2 years, 42% of patients remained on study, the authors reported. Discontinuation was caused by progressive disease (21%), lack of efficacy (5%), possibly or probably ponatinib-related deaths (n = 20; 5%), and adverse events (14%)—most commonly, thrombocytopenia (14%), the researchers reported.

“Response rates were higher in CP-CML T315I versus resistant/intolerant cohorts, however, a post-hoc multivariate analysis previously showed that T315I was not an independent predictor of MCyR,” the authors cautioned. “Other features, especially higher dose intensity and younger age in T315I patients, may explain the higher response rates.”

CP-CML patients’ responses “were deep and durable,” the authors reported, with 91% of patients experiencing MCyR maintained at 12 months. Progression-free survival (PFS) and overall survival (OS) were 80% and 94% at 12 months, respectively, they noted.

“Pancreatitis was the most common drug-related serious AE” at 6%, the authors reported. It “occurred early and was primarily managed with dose modification.” One patient discontinued participation in the study, as a result.

Serious cardiovascular, cerebrovascular, and peripheral vascular adverse events also occurred in 1% to 2% of patients.

“Ponatinib is an important treatment for patients in whom the need and potential benefit outweigh the potential risk,” the authors concluded.

The authors disclosed several consultancy and research funding sources from Bristol Myers Squibb, Ariad, Pfizer, Novartis, Teva, and other pharmaceutical companies.


  1. Cortes JE et al. Abstract #632. Presented at: American Society of Hematology Meeting 2013. Dec. 7-10, 2013; New Orleans.