Five-year cardiovascular outcomes in patients with chronic myeloid leukemia treated with imatinib, dasatinib or nilotinib: data from a large multinational collaborative network

Abstract

Abstract Background BCR-ABL tyrosine kinase inhibitors (TKI) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, concern has arisen about the cardiac safety profile of these drugs. Purpose To compare long-term risks of adverse cardiovascular and cerebrovascular events (ACE), heart failure or left ventricular ejection fraction (LVEF) <50% and venous thromboembolic events (VTE) in patients with CML treated with first-line Bcr-ABL TKIs, using data from a large multinational network. Methods Patients aged ≥18 years with chronic myeloid leukemia treated with imatinib or dasatinib or nilotinib and without prior cardiovascular or cerebrovascular disease. We used propensity score matching to balance the cohorts. The 5-year cumulative incidences and hazard ratios were calculated. Results We identified 3,722 patients with CML under treatment with Imatinib (n=1,906), Dasatinib (n=1,269) and Nilotinib (n=547). Patients with imatinib compared to dasatinib showed higher risk for ACE (hazard ratio 2,13, 95% IC 1.15–3.94, p=0.016). Patients with imatinib presented lower risk than nilotinib for ACE (hazard ratio 0.50, 95% IC 0.30–0.83, p=0.0074). In relation to heart failure or LVEF <50%, patients with imatinib had higher risk than dasatinib (hazard ratio 9.41, 95% IC 1.22–72.17, p=0.03), but no significant difference was observed between imatinib and nilotinib (hazard ratio 0.48, 95% IC 0,215–1.01, p=0.064). The probability of survival (Kaplan Meier curves) without ACE, heart failure or LVEF <50% and VTE are depicted in the Central Illustration. Conclusions In a large cohort of patients with CML, those treated with nilotinib had higher 5-year risk of adverse cardiovascular and cerebrovascular events, while patients with dasatinib showed lower risk than patients with imatinib. The risk of heart failure was higher in patients with imatinib than in patients with dasatinib, but not when compared to nilotinib. Funding Acknowledgement Type of funding sources: None.