Cardiovascular toxicity in patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors in the real-life practice: Identification of risk factors and the role of prophylaxis

Cardiovascular adverse events (CV-AE) represent emerging complications in chronic myeloid leukemia (CML) treated with second-generation tyrosine kinase inhibitors (2ndGTKIs). Current recommendations highlight the importance of a careful evaluation of CV risk factors but the role of a primary prophylaxis with aspirin is still matter of debate. We evaluated 506 adult CML patients (mean age 52, range 18-87) who started nilotinib (286) or dasatinib (220) in first o subsequent lines of treatment from Jan 2012 to Dec 2015. CV diseases (CVD) and risk factors, primary and secondary prophylaxis, and management of CV-AE were assessed at baseline and during treatment. Anamnesis for CVD was positive in 181 (35.8%) patients. The 60-month CV-EFS was 78.3%. Patients treated with nilotinib or dasatinib showed a CV-EFS of 75.3% and 83.6%, respectively (p=NS). Positive anamnesis for CVD (p=0.001) and 2ndGTKI line of treatment >1 (p=0.002) were significantly associated to higher incidence of CV-AE. Patients with both 2 risk factors (CML-CV high score) showed a CV-EFS significantly lower (54.1±8.2% vs 83.7±4.4% and 81.3.±3.9%, p<0.001). The atherothrombotic EFS was 86.9±2.5%. No significant difference was found in patients underwent aspirin prophylaxis before starting 2ndGTKIs. Considering only patients with CML-CV high risk score, atherothrombotic EFS was significantly higher in patients treated with aspirin (100 % vs 66.1± 9.5%; p=0.11). Management of CV-AE required additional tests, medical therapy and invasive procedures. In conclusion our findings emphasize the need to personalize prevention strategies based on CV risk factors, particularly in those patients with positive anamnesis for CVD and 2ndGTKI line of treatment