Cardiovascular Issues in Tyrosine Kinase Inhibitors Treatments for Chronic Myeloid Leukemia: A Review

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by a fusion gene, encoding for the chimeric protein BCR-ABL, with constitutive tyrosine kinase activity. The use of tyrosine kinase inhibitors (TKIs) has drastically improved survival, but there are significant concerns about cardiovascular toxicity. Cardiovascular risk can be lowered with appropriate baseline evaluation, accurate choice of TKI therapy, improvement of modifiable cardiovascular risk factors through lifestyle modifications, and prescription of drugs for primary or secondary prevention. Which examinations are necessary, and when do they have to be scheduled? How often should a TKI-treated patient undergo which cardiology test or exam? Is there an accurate way to estimate the risk that each TKI may determine a cardiovascular adverse event in a CML patient? In a few words, how can we optimize the cardiovascular risk management in CML patients before and during TKI treatment? The aim of this review is to describe cardiac and vascular toxicity of TKIs used for CML treatment according to the most recent literature and to identify unmet clinical needs in cardiovascular risk management and complications in these patients. Regarding the TKI-induced cardiovascular toxicity, the full mechanism is still unclear, but it is accepted that different factors may play different roles: endothelial damage and atherosclerosis, metabolic impairment, hypertensive effect, glomerular impairment, and mast-cell disruption. Preventive strategies are aimed at minimizing cardiovascular risk when CML is diagnosed. Cardio-oncology units in specialized hematology centers may afford a personalized and multidisciplinary approach to the patient, optimizing the balance between treatment of the neoplasm and management of cardiovascular risk.

Combined Effects of 2-Methoxyestradiol (Hypoxia-Inducible Factor 1α Inhibitor) and Dasatinib (A Second-Generation Tyrosine Kinase Inhibitor) on Chronic Myelocytic Leukemia Cells

“…Tyrosine kinase inhibitor (TKI) is introduced as a targeted therapy drug, namely, imatinib, nilotinib, and dasatinib, which benefits 85% to 90% of CML patients with a 10-year survival rate. Unfortunately, the extensive administration of TKI has brought about increasing drug resistance problems in CML patients [ 2 ]. Therefore, it is of vital significance to explore novel therapeutic targets and targeted medication for CML to further improve the therapeutic level of CML.…”

Update on cancer therapy-induced atherosclerosis

“…Endothelial damage (increase in proatherogenic surface molecules and VEGFR inhibition), metabolic impairment, mast-cell disruption (KIT inhibition), and the development of hypertension (VEGFR inhibition) may all play a role in the increase in adverse CV effects of these agents [5 ▪ ]. Nilotinib administration to atherogenic mice increased atherosclerotic buildup and blocked reperfusion and angiogenesis after arterial occlusion [7].…”

Cardiovascular adverse events in chronic myeloid leukemia patients treated with nilotinib or imatinib: A systematic review, meta-analysis and integrative bioinformatics analysis

“…Apart from hematological, musculoskeletal, gastrointestinal and subcutaneous toxicity, nilotinib can also lead to adverse effects different from those of imatinib, such as cardiovascular adverse events ( 1 , 6 ). A total of 23.3% of patients have at least one arterial obstructive event, which suggests that cardiovascular toxicity remains a concern.…”