Arterial occlusive events (AOEs) represent emerging complications in chronic myeloid leukemia (CML) patients treated with ponatinib. We identified 85 consecutive CML adult patients who were treated with ponatinib in 17 Italian centers. Patients were stratified according to the Systematic Coronary Risk Evaluation (SCORE) assessment, based on sex, age, smoking habits, systolic blood pressure, and total cholesterol levels. The 60‐month cumulative incidence rate of AOEs excluding hypertension was 25.7%. Hypertension was reported in 14.1% of patients. The median time of exposure to ponatinib was 28 months (range, 3‐69 months). Patients with a high to very high SCORE risk showed a significantly higher incidence rate of AOEs (74.3% vs 15.2%, P < 0.001). Patients aged ≥60 years showed a significantly higher incidence rate of AOEs (51.5% vs 16.9%, P = 0.008). In multivariate analysis, no association was found between AOEs and positive history of CV disease, age, dose of ponatinib, previous exposure to nilotinib, and comorbidities. Only the SCORE risk was confirmed as a significant predictive factor (P = 0.01; HR = 10.9; 95% C.I. = 1.7‐67.8). Patients aged ≥60 years who were treated with aspirin had a lower incidence rate of AOEs (33.3% vs 61.8%). Among the 14 reported AOEs, 78.6% of them showed grade 3 to 4 toxicity. This real‐life study confirmed the increased incidence of AOEs in CML patients treated with ponatinib, with high to very high SCORE risk. We suggest that patients aged ≥60 years who were treated with ponatinib should undergo prophylaxis with 100 mg/day of aspirin. Our findings emphasize personalized prevention strategies based on CV risk factors.

Long-term treatment with the second-generation tyrosine kinase inhibitors (2 ndG TKIs) nilotinib and dasatinib may result in cardiovascular (CV) complications. Accumulating evidence suggests that the combination of a median age at the time of chronic myeloid leukemia (CML) diagnosis of greater than 60 years, when CV adverse events (AEs) are common, and the CV toxicity of 2 ndG TKIs represents per se a potential predisposing factor, which requires preventive strategies and CV surveillance in patients with CML. 1-3 Previous studies have suggested the usefulness of the systematic coronary risk evaluation (SCORE) assessment at disease baseline, a 10-year risk estimation of fatal CV disease based on sex, age, smoking habits, systolic blood pressure, and total cholesterol levels, to identify patients who are at heightened risk of CV AEs during nilotinib treatment. 4,5 A preventive strategy with primary prophylaxis based on aspirin remains under discussion. We therefore analyzed a large real-life cohort of Italian patients with CML treated with a 2 ndG TKIs as first-or subsequent-line of treatment. The primary objective was to evaluate the incidence of CV AEs and the association with the SCORE assessment and other baseline risk factors. The secondary objectives were to evaluate the role of primary prophylaxis in preventing CV atherothrombotic events.We identified consecutive adult patients with CML who initiated nilotinib or dasatinib as first-or subsequent-line treatment, between January 2012 and December 2015 in 20 Italian centers. Patients were stratified into low-moderate (SCORE 5%) or high-very high (SCORE >5%) CV risk. Additional risk factors were the presence of diabetes, body mass index > 24.5 kg/m 2 , mild or severe renal insufficiency, and dyslipidemia. Patients were also evaluated for comorbidities and a positive anamnesis of CV diseases, including angina, myocardial infarction, stroke, heart failure, arterial hypertension, cardiomyopathy, heart arrhythmia, valvular heart disease, aortic aneurysms, ischemic cerebrovascular events, peripheral artery disease, thromboembolic disease, and venous thrombosis. The presence of antithrombotic prophylaxis before initiating CML treatment was also recorded. The probability of the cumulative incidence of CV and atherothrombotic AEs was estimated after initiating treatment with 2 ndG TKIs. The cumulative incidence of deep molecular response (MR 4 ) was evaluated from the initiation of 2 ndG TKIs treatment. Multivariate analyses were performed using the Cox proportional hazards regression model. A total of 506 patients with CML were retrospectively recruited. The patients' characteristics are shown in Supporting Information Table S1.The mean age at diagnosis was 52 years (range 18-87) and 57% were men. Sokal score was intermediate-high in 55% of patients. The mean follow-up time since CML diagnosis was 5.4 years (range 0.2-23). Overall, 286 patients were treated with nilotinib and 220 with dasatinib. 2 ndG TKIs were administered as first-, second-, and third-line treatme...

No abstract

No abstract

No abstract