Vascular safety issues in CML patients treated with BCR/ABL1 kinase inhibitors

Blood. 2015 Feb 5;125(6):901-6. doi: 10.1182/blood-2014-09-594432. Epub 2014 Dec 18.

Abstract

Vascular safety is an emerging issue in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs). Whereas imatinib exhibits a well-documented and favorable long-term safety profile without obvious accumulation of vascular events, several types of vascular adverse events (VAEs) have been described in patients receiving second- or third-generation BCR/ABL1 TKIs. Such VAEs include pulmonary hypertension in patients treated with dasatinib, peripheral arterial occlusive disease and other arterial disorders in patients receiving nilotinib, and venous and arterial vascular occlusive events during ponatinib. Although each TKI interacts with a unique profile of molecular targets and has been associated with a unique pattern of adverse events, the mechanisms of drug-induced vasculopathy are not well understood. Here, recent data and concepts around VAEs in TKI-treated patients with CML are discussed, with special reference to potential mechanisms, event management, and strategies aimed at avoiding occurrence of such events in long-term treated patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fusion Proteins, bcr-abl / antagonists & inhibitors*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / complications
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Protein Kinase Inhibitors / adverse effects*
  • Vascular Diseases / chemically induced*
  • Vascular Diseases / complications

Substances

  • Protein Kinase Inhibitors
  • Fusion Proteins, bcr-abl