Management of vascular adverse events during tyrosine kinase inhibitors in patients with chronic myeloid leukemia

Abstract

In 2000, imatinib became the first tyrosine kinase inhibitor (TKI) approved for the treatment of chronic myeloid leukemia (CML); this was soon followed by second generation (nilotinib, dasatinib, and bosutinib) and third generation (ponatinib) TKIs, all of which are currently available for the treatment of CML. Their emergence has revolutionized treatment strategies for CML, leading to a new era that has seen the 10-year overall survival rate for CML patients exceed 80%; despite the impact of TKIs on CML prognosis, only 10 to 20% of CML patients maintain treatment-free remission after TKI cessation. Moreover, prolonged treatment produces various adverse effects, such as serious vascular adverse events including stroke, myocardial infarction, and peripheral arterial occlusive disease. The pathophysiological mechanisms underlying those effects remain unclear, and protocols for managing such life-threatening events have not been established. Thus, I conducted a narrative review of the literature to clarify the current state of knowledge. Based on that review and my experiences during daily clinics, I herein present a discussion on the incidence, diagnosis, and management of TKI-induced vascular adverse events.