Cardiovascular Toxicity Associated With Tyrosine Kinase Inhibitor Therapy In Chronic Myeloid Leukemia.

Abstract

Treatment of Chronic myeloid leukemia (CML) typically entails a long-term course of tyrosine kinase inhibitors (TKI) therapy. This review provides a summary on the cardiotoxic effects of TKIs. Five small molecular TKIs were evaluated in our review. The cardiotoxic effects of TKIs can range from superficial edema to potentially fatal conditions such as congestive heart failure (HF) and acute coronary syndrome (ACS). With the constant introduction of newer generations of TKIs, it has been demonstrated that different TKIs have distinct cardiovascular safety profiles. Amongst which, the first-generation TKI - imatinib appears to have the safest profile, mainly causing edema along with nausea, rash and muscle cramps. Other TKIs, like the second-generation dasatinib, bosutinib,and nilotinib, have shown an increased incidence of pleural effusion and QT prolongation. Ponatinib, a third generation TKI, has shown a relatively high incidence of serious adverse effects including thrombotic vascular occlusion and heart failure, particularly in patients with a prior history of cardiovascular impairment. Therefore, it is advisable that at-risk patients taking TKIs be screened with an Electrocardiogram (ECG) and have a careful cardiovascular risk assessment before starting TKI therapy to avoid potential cardiotoxic effects such as arrhythmias, acute coronary syndrome (ACS), congestive heart failure, and pleural effusion. Keywords: tyrosine kinase inhibitor, TKI, chronic myelogenous leukemia, CML, cardiotoxicity, side effects, imatinib, dasatinib, bosutinib, nilotinib, ponatinib.