Long-term mortality rate for cardiovascular disease in 656 chronic myeloid leukaemia patients treated with second-and third-generation tyrosine kinase inhibitors

Introduction: Cardiovascular (CV) diseases represent the leading cause of premature death, responsible for 35% of deaths under 75 years and 29% of deaths under 65 years, being ischemic heart disease (IHD) the leading single cause. Limited information is available regarding the rate of long-term CV mortality in chronic myeloid leukemia (CML) patients treated in the real-life practice with second- and third-generation tyrosine kinase inhibitors (2ndG/3rdG TKIs) nilotinib, dasatinib, bosutinib and ponatinib. The primary endpoint of this study was to establish the incidence of mortality related to CV adverse events and the PYLL parameter in a Italian cohort of CML patients. The secondary endpoint was to evaluate the standardized mortality ratio (SMR) following IHD. Methods: We considered 656 adult CP-CML patients diagnosed and treated consecutively with 2ndG/3rdG TKI, frontline or with subsequent lines of treatment in 19 Italian centres, between 2012 and 2017. The CV-free survival was estimated from diagnosis to the date of death occurred for CV complications. PYLL to CV disease provided a measure of premature mortality and was calculated by summing-up deaths occurring at each age and multiplying that result by the number of the remaining years up to the selected age limit of 75 years. The SMR was used to compare the mortality risk following IHD of the cohort of CML patients to that of the Italian population. An SMR greater than 1.0 indicates that there were “excess deaths” compared to what was expected. Results: Overall 37 deaths were recorded. The 15-year OS was 83.3±3.6%. No significative difference in OS was observed according to the TKI administered. The 15-year CV-mortality free survival was 93±2.8% (Figure 1). Age ≥65 years (p=0.005) and a positive history of CV disease (p=0.04) were significantly associated to a lower CV-mortality free survival. CV disease accounted 16.5% and 5% of potential years of life lost (PYLL) in male and female patients, in comparison with 18% and 12% of Italian population, respectively. The standard mortality ratio (SMR) following ischemic heart disease (IHD) was 3.9 in males and 3.8 in female patients with excess deaths observed in comparison with the population of control. Conclusions: Although life expectancy in CML is close to that observed in the general population, our data are a reminder that IHD remains an important cause of death in CML patients treated with 2ndG/3rdG TKIs. These findings emphasize the need to personalize prevention strategies based on CV risk.