Impact of TKI Switching, Reduction, and Discontinuation on Cardiovascular Events in cml patients

Abstract

Abstract The development of tyrosine kinase inhibitors (TKIs) has dramatically improved the treatment outcomes of the chronic myelogenous leukemia-chronic phase (CML-CP). However, cardiovascular events (CVEs), such as hypertension, peripheral arterial occlusive disease, pulmonary arterial hypertension, and cerebral infarction, continue to occur, which highlights the need to develop preventive monitoring and treatment strategy for adverse vascular events. This study retrospectively analyzed the data on CVEs in 63 patients with chronic myeloid leukemia treated with TKIs at our institution. TKI treatments were discontinued in 1 patient and 16 patients owing to serious CVEs and adverse events other than CVEs, respectively. This study showed that male patients tended to experience more abnormal findings on cardiovascular examination and minor CVEs with increasing age than female patients. No prolongation of QT interval was observed. During follow-up, improvements in tricuspid regurgitant pressure gradient and brain natriuretic peptide values and hypertension were observed after reducing the dose of the same TKI, interrupting the TKI treatment, and switching from the second-and third-generation TKIs to imatinib (IM) or bosutinib (BOS). These data suggest the importance of CVE prevention via blood pressure control and cardiovascular examination in CML patients at high risk for CVE. Rapid intervention under the cooperation of a cardiologist is also essential when CVEs develop. The CVE risk may be decreased by switching to IM or BOS or via TKI dose reduction/interruption in patients in whom DMR is achieved. However, further studies with more patients are required.