Ponatinib: A Review of Efficacy and Safety

Abstract

Ponatinib is a third generation kinase inhibitor designed to overcome the gatekeeper T315I mutation. In different trials this drug showed inhibitory activity against native BCR-ABL1 kinase and several ABL1 mutations. For this reason, ponatinib is currently indicated for the treatment of chronic myeloid leukaemia (CML) in every phase of disease resistant and/or intolerant to dasatinib and nilotinib and for whom imatinib is not indicated anymore or for patients with T315I mutation. The drug is also indicated for Ph+ acute lymphoblastic leukaemia (ALL). Ponatinib was temporarily suspended in 2013 for the occurrence of cardiovascular thrombotic events. Since then, different investigators analyzed baseline characteristics of patient candidates for ponatinib, especially cardiovascular profile, in order to describe general management recommendations in this setting. In this review, clinical trials data about the use of ponatinib in CML and Ph+ ALL patients will be discussed. It will be focused also about the safety and tolerability profile of the drug and future perspectives of employment.

Keywords: Chronic myeloid leukemia; EPIC trial; PACE trial; Ph+ acute lymphoblastic leukemia; T315I mutation; cardiovascular events; ponatinib..