Ponatinib resulted in durable responses after 4 years in heavily pretreated patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL), updated findings presented at the 2016 American Society of Clinical Oncology (ASCO) meeting have shown.1

Ponatinib is an approved tyrosine kinase inhibitor with potent activity against native and resistant BCR-ABL, including the T315I mutation. The safety and efficacy of ponatinib were evaluated in the pivotal PACE trial, which enrolled 449 patients with CML or Ph+ ALL refractory to dasatinib or nilotinib, or with T315I.

Results showed that responses continued to deepen over time despite dose reductions. At year 1, the complete cytogenetic response rate was 51% among the 267 evaluable patients with CML in chronic phase; the major molecular response rate was 30%. At year 4, the complete cytogenetic response rate and major molecular response rates were 54% and 39%, respectively.

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Researchers found that the estimated 4-year progression-free survival rate was 56%, the estimated 4-year overall survival rate 77%, and maintenance of major cytogenetic response and major molecular response were 82% and 61%, respectively.

Nearly 2 years after recommended dose reductions, 87% and 74% of patients with chronic phase CML were estimated to maintain major cytogenetic response and major molecular response, respectively.

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The most frequently reported ponatinib-related adverse events were thrombocytopenia, abdominal pain, rash, constipation, headache, dry skin, fatigue, and hypertension.

Twenty-three percent of patients experienced an arterial occlusive event and 19% reported a serious event of this kind. A total of 8% of all dose-reduced patients without a prior arterial occlusive event on trial experienced an event, suggesting that the number of newly-occurring arterial occlusive events has decreased.


1. Cortes JE, Pinilla-Ibarz J, Le Coutre PD, Paquette R, Chuah C, Nicolini FE, et al. 4-year results of the ponatinib phase II PACE trial in patients (pts) with heavily pretreated leukemia. J Clin Oncol. 2016; 34 (suppl; abstr 7013).