Long-Term Data Show Ponatinib Effective, With Thrombotic Risk in CML

Ponatinib demonstrates continuing clinical activity in chronic-phase chronic myeloid leukemia patients who failed prior treatment with other TKIs.

Long-term results of a phase I trial show that ponatinib has continuing clinical activity in patients with chronic-phase chronic myeloid leukemia (CML) who failed prior treatment with other tyrosine kinase inhibitors (TKIs) (abstract 7047); the drug carries some vascular safety concerns that have resulted in early trial closures in the past. Results were presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting held May 29 to June 2 in Chicago.

Studies have indicated that ponatinib carries an increased risk of thrombotic events. The US Food and Drug Administration (FDA) requested a suspension of marketing in 2013 and has required certain measures from the manufacturer regarding its safety.

The newly reported results are from a phase I trial of heavily pretreated patients with resistant or intolerant CML or Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL). The trial enrolled 81 patients in total, 43 of whom had CML; 60% of those patients had failed at least three prior TKIs, and 98% had received at least two prior TKIs. As of data cutoff in February, 22 patients (51%) remained on study.

After a median follow-up of 53.1 months, 72% of chronic-phase CML patients achieved a major cytogenetic response (MCyR); 65% achieved a complete cytogenetic response, and 56% achieved a major molecular response. Of the 22 patients still on study, 17 (77%) were in ongoing deep molecular response.

Patients with a T315I mutation fared particularly well: One of 12 patients discontinued, and 10 of the other 11 achieved a MCyR and 8 of those 10 were in continuous MCyR.

The vascular problems found with ponatinib were also seen to some degree in these patients. Thirteen patients (30%) experienced a serious arterial occlusive event (AOE), and 40% experienced an AOE of any severity. Two patients had a venous thromboembolic event (VTE), though none were serious. No patient death was attributed to AOE or VTE.

“With more than half of the chronic-phase CML patients still on study after a minimum of 4 years, ponatinib continues to maintain anti-leukemic responses in this heavily pretreated patient population,” said lead author Moshe Talpaz, MD, of the University of Michigan Comprehensive Cancer Center, according to a press release. “We are continuing to study the profile of ponatinib and the impact of dose reductions in patients with CML and Ph+ [Philadelphia chromosome–positive] ALL for whom there are limited treatment options and the potential benefit outweighs the risk.”