Recurrent arterial occlusive events in patients with chronic myeloid leukemia treated with second- and third-generation tyrosine kinase inhibitors and role of secondary prevention

Background: Risk of death is particularly high in patientswith a previous history of arterial occlusive events (AOEs) and the probability for a recurrent event is around 20\%. Little is known about recurrent AOE and the role of secondary prevention in patients with Chronic Myeloid Leukemia (CML) with previous AOE, treated with secondand third-generation tyrosine kinase inhibitors (2ndG/3rdG TKIs), nilotinib, dasatinib, bosutinib and ponatinib. Methods: We identified a real-life cohort of 57 consecutive adult CML patients treated with 2ndG/3rdG TKI. All patients had a previous history of AOE. Ongoing use of secondary prevention of AOE (including antiplatelet agents, anticoagulant therapy, and statins) before starting a 2ndG/3rdG TKI was recorded, as well as CV risk factors. Results: The 60-month cumulative incidence rate of recurrent AOEswas 47.8 +/- 10.9\%. Despite a history of AOE, 10 patients (16\%) were not receiving secondary preventativemeasures. Patients treatedwith nilotinib and ponatinib showed a higher incidence of recurrent AOEs (76.7 +/- 14.3\% and 64 +/- 20.1\%, respectively) than those treatedwith dasatinib and bosutinib (44 +/- 24.2\% and 30.5 +/- 15.5\%, respectively) (p= 0.01). Only treatmentwith a 2ndG/3rdG TKI given as second or subsequent line therapy showed a significant association with an increased incidence of recurrent AOE (p = 0.039). Overall, 17 recurrent AOEs were observed; 3 CV-related deaths were reported. Conclusion: CML patientswith a previous history of AOE treated with 2ndG/3rdG TKI represent a particular patient population with a higher probability of experiencing a recurrent AOE; individualized treatment is needed to optimize secondary prevention. (c) 2019 Elsevier B. V. All rights reserved.