Endothelial function in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors is not related to cardiovascular risk assessed by SCORE2 algorithm.

Abstract

Tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia (CML) but are endowed with negative effects on endothelial function. To characterize endothelial function in patients with CML treated with various TKIs. Forty-eight patients diagnosed with chronic phase CML treated with TKIs, such as imatinib, bosutinib, nilotinib, ponatinib, and asciminib were included. Endothelial function was assessed in the brachial artery and microcirculation based on flow-mediated dilation (FMD), reactive hyperemia peripheral arterial tonometry (RH-PAT) and Flow Mediated Skin Fluorescence (FMSF). Reactive Hyperemia Index (RHI), FMD [%], Reactive Hyperemia Response (RHR [%]), Normoxia Oscillatory index (NOI [%]) and Hyperemic Response index (HR index [%]) did not differentiate between the group of patients with low / moderate risk in the Systemic Coronary Risk Estimation 2 (SCORE2), SCORE2-Older Persons (SCORE2-OP) and those with high / very high-risk scores. Among patients with low/intermediate risk based on the SCORE2 algorithms, some had lower (<Q1) values of endothelial parameters, reflecting impaired endothelial function, when compared with the whole population. Lower values of endothelial function parameters were associated with overall long-term treatment with TKIs or ponatinib treatment. Importantly, endothelial function assessed by FMSF (RHR [%]) negatively correlated with the total duration of TKI treatment, also after adjustment for age. Endothelial function in CML patients treated with TKIs was not related to cardiovascular risk based on SCORE2/SCORE2-OP algorithms but CML-specific factors, including duration of TKI treatment. FMSF-based assessment of skin microcirculation was a sensitive method for detecting the vascular effects of TKIs.