CARDIOVASCULAR TOXICITY IN CHRONIC MYELOID LEUKEMIA PATIENTS TREATED WITH SECOND-GENERATION TYROSINE KINASE INHIBITORS IN REAL-LIFE PRACTICE. IDENTIFICATION OF RISK FACTORS AND ROLE OF PROPHYLAXIS

Background: Cardiovascular adverse events (CV-AE) represent emerging complications in chronic myeloid leukemia (CML) patients 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 a matter of debate. Aims:We therefore analyzed a large real-life cohort of Italian CML patients treated with a 2ndGTKIs as first or subsequent line of treatment. The primary objective was to evaluate the incidence of CV-AE and the association with the Systematic Coronary Risk Evaluation (SCORE) assessment and other baseline risk factors. Secondary objective were to evaluate the role of primary or secondary prophylaxis in preventing CV atherothrombotic events and to report the management of CV-AE complications in the clinical practice. Methods: We evaluated 506 adult CML patients (mean age 52, range 18-87) who were treated with nilotinib (286) or dasatinib (220) as first or subsequent lines of treatment between January 2012 and December 2015. CV diseases (CVD) and risk factors, primary and secondary prophylaxis, and management of CV-AE were assessed at baseline and during treatment. Results: Anamnesis for CVD was positive in 181 (35.8%) patients. The 60-month cumulative CV-AE incidence was 21.7%. Patients treated with nilotinib or dasatinib showed a CV-AE incidence of 24.7% and 16.4%, respectively (p=NS). A positive history for CVD (p=0.001) and a 2ndGTKI line of treatment >1 (p=0.002) were significantly associated to a higher incidence of CV-AE. Patients with both 2 risk factors (CML-CV high risk score) showed a CV-AE incidence significantly higher (45.9% vs 16.3% and 18.7%, p<0.001) (Figure 1). The atherothrombotic AE incidence was 13.1%. No significant difference in atherothrombotic AE incidence was found in patients who underwent aspirin primary prophylaxis before starting 2ndGTKIs. Considering only patients with age>60 years and CML-CV high risk score, atherothrombotic AE incidence was significantly lower in those treated with aspirin (0% vs 58.2%; p=0.01). Summary/Conclusion: This study confirmed the increased risk of CV-AE in CML patients treated with 2ndGTKIs in the real-life, particularly in those patients with positive anamnesis for CVD and 2ndGTKI line of treatment >1. Our findings emphasize the need of personalized prevention strategies based on CV risk factors; ideally, management and treatment of these patients should be performed in close collaboration with cardio-oncologists, angiologists and vascular surgeons. We suggest that patients with age >60 years and CV diseases undergoing a 2ndGTKI line treatment >1 are likely to be the best candidates to aspirin. Data on efficacy of primary prophylaxis in CV-CML high risk patients should be confirmed in prospective randomised trials