Mechanisms, Clinical Phenotype and Potential Risk Prediction for Cardiovascular Toxicity Induced by Tyrosine Kinase Inhibitors In Chronic Myeloid Leukemia.

Source: PubMed, NCBI / U.S. National Library of Medicine

Tyrosine kinase inhibitors (TKIs) form the cornerstone of targeted therapy for chronic myeloid leukemia (CML), significantly improving patient prognosis. However, long-term use of TKIs, particularly second-generation (e.g., nilotinib) and third-generation (e.g., ponatinib) drugs, has led to adverse cardiovascular events (CV-AEs). CV-AEs pose a critical challenge to patients' long-term quality of life and treatment adherence. This narrative review systematically elucidates the complex mechanisms underlying TKI-induced cardiovascular toxicity and proposes the "Metabolism-Endothelium-Thrombosis Axis" as a unifying conceptual framework, integrating endothelial dysfunction, metabolic impairment, oxidative stress, inflammatory responses, and abnormal platelet activation into a coherent pathophysiological cascade. These mechanisms collectively contribute to a spectrum of clinical phenotypes. At the clinical management level, identifying individuals at high risk is crucial. Multiple risk prediction models demonstrate predictive value for CV-AEs, particularly arterial occlusive events (AOEs). Future research should focus on elucidating TKI-specific toxicity pathways, validating and optimizing risk prediction models, and exploring effective cardioprotective strategies. Ultimately, this work will maximize cardiovascular risk reduction while preserving antileukemic efficacy.