Tyrosine Kinase Inhibitors in Leukemia and Cardiovascular Events: From Mechanism to Patient Care

Abstract

Targeted oncology therapies have revolutionized cancer treatment over the last decade and have resulted in improved prognosis for many patients. This advance has emanated from elucidation of pathways responsible for tumorigenesis followed by targeting of these pathways by specific molecules. Cardiovascular care has become an increasingly critical aspect of patient care in part because patients live longer, but also due to potential associated toxicities from these therapies. Because of the targeted nature of cancer therapies, cardiac and vascular side effects may additionally provide insights into the basic biology of vascular disease. We herein provide the example of tyrosine kinase inhibitors utilized in chronic myelogenous leukemia to illustrate this medical transformation. We describe the vascular considerations for the clinical care of chronic myelogenous leukemia patients as well as the emerging literature on mechanisms of toxicities of the individual tyrosine kinase inhibitors. We additionally postulate that basic insights into toxicities of novel cancer therapies may serve as a new platform for investigation in vascular biology and a new translational research opportunity in vascular medicine.

Keywords: leukemia, myelogenous, chronic, BCR-ABL positive; patient care; peripheral arterial disease; prognosis; tyrosine kinase.

Figure 1 –

Mechanism of action of BCR-ABL tyrosine kinase in CML (Left). Mechanism of action of TKI in treatment of CML.(Right) ATP: Adenosine triphosphate; ADP: Adenosine diphosphate; P: phosphate; CML: Chronic myelogenous leukemia; TKI: Tyrosine kinase inhibitor.

Figure 2 –

Clinical recommendations for assessment of cardiovascular toxicity in individuals with chronic myelogenous leukemia receiving kinase inhibitors. ✔ Recommended; ✕ as clinically indicated; Assess the QT prolongation. If there are any signs in favor of pulmonary arterial hypertension like dyspnea, consider echocardiogram as first line of screening.

Figure 3 -

“ABCDE” approach, which has been proposed to reduce CV disease in patients with CML receiving TKI treatment. CML, chronic myeloid leukemia; CV, cardiovascular; TKI, tyrosine kinase inhibitor; ABI, ankle brachial index; BP, blood pressure; HTN, hypertension; ACEI, angiotensin-converting-enzyme inhibitors; ARB, angiotensin receptor blocker; BBs, beta blockers; dp-CCB, dihydropyridine calcium channel blockers; ndp-CCB, non-dihydropyridine calcium channel blockers.