The frequency of cardiovascular events caused by second-generation tyrosine kinase inhibitors may depend on the treatment intensity in patients with chronic myeloid leukemia

Abstract Second-generation tyrosine kinase inhibitors (2GTKIs) have not improved overall survival compared to imatinib due to an increase in cardiovascular events (CVEs) and deaths unrelated to chronic myeloid leukemia (CML). We retrospectively analyzed the incidence of CVEs among CML patients treated with TKIs at our institution and analyzed the risk factors for CVEs. Method and results: Fifty-nine newly diagnosed CML patients were included. Imatinib, nilotinib, dasatinib, bostinib, and ponatinib were given to 29, 34, 21, 3, and 4 patients, respectively. The cumulative incidence of CVEs was 16.1% at 5 years and 32.4% at 10 years. According to the univariate analysis, a history of vascular events (p=0.046) and the presence of any risk factor for atherosclerotic disease (p=0.046) were significant, and nilotinib (p=0.053) tended to increase the risk of CVEs. According to the multivariate analysis, nilotinib (p<0.001) and a history of vascular events (p=0.04) were significant risk factors for CVEs, but dasatinib tended to decrease the risk of CVEs (p=0.17, hazard ratio (HR)=0.26, 95% CI 0.04-1.76). The only significant difference between nilotinib and dasatinib was the dose intensity of each TKI (1.0 vs 0.5, p=0.001). Conclusion: In addition to existing interventions targeting atherosclerotic factors, response-adapted dose adjustments may be necessary to reduce CVEs.