Cardiovascular risk assessments in chronic myeloid leukemia allow identification of patients at high risk of cardiovascular events during treatment with nilotinib

Abstract

Cardiovascular risk assessments in chronic myeloid leukemia allow identification of patients at high risk of cardiovascular events during treatment with nilotinibTo the Editor Nilotinib, a second-generation tyrosine kinase inhibitor, has been approved at the dose of 300 mg bis in die (BID) for newly diagnosed chronic phase chronic myeloid leukemia patients and at the dose of 400 mg BID for chronic or accelerated phase patients with resistance or intolerance to imatinib [1]. In the last few years, several communications of arterial thrombotic events have been described during nilotinib therapy, but the exact pathogenetic mechanisms are still unknown [2]. In the ENESTnd trial at the last follow-up of 5 years, an increased rate of ischemic events with nilotinib has been reported (6.8% with nilotinib 300 mg BID and 12.6% with nilotinib 400 mg BID) as compared to imatinib (2.1%) [3]. Thus, it has become of great importance to evaluate the benefit/risk ratio at baseline, considering the overall cardiovascular risk profile of patients, taking into account pre-existing comorbidities and risk factors predisposing to atherosclerotic events.Our group and other investigators tried to retrospectively apply the European 2012 cardiovascular risk assessment model (SCORE chart) in order to identify patients at risk of atherosclerotic events during nilotinib treatment: both studies were able to demonstrate the validity of the ESC criteria to select patients at risk of cardiovascular events during treatment [4,5]. According to these ESC 2012 criteria, patients were stratified on the basis of age, sex, systolic pressure, smoking, and total cholesterol level [6]. Indeed, other prognostic scores already existed: the Framingham risk score [7] which is a sex-specific algorithm developed in 1998 in order to calculate the 10-year cardiovascular individual risk. It was then modified and updated to include dyslipidaemia, age, hypertension treatment, smoking, total cholesterol level, with exclusion of diabetes, that was included in the first version, because this risk factor was considered to be a coronary heart disease equivalent. Another prediction algorithm for cardiovascular disease is the QRisk2 [8] that uses traditional risk factors such as age, systolic pressure, smoking status, a ratio of total serum cholesterol to high-density lipoprotein cholesterol, but also the body mass index, ethnicity, family history, chronic kidney disease, rheumatoid arthritis, atrial fibrillation, diabetes, and anti-hypertensive treatment. A QRisk2 over 10%, indicating 10% risk of cardiovascular disease event over the next ten years, suggests that a therapy with lipid lowering therapy with a statin should be started. We retrospectively applied these two latter prognostic score to the same population of CML patients treated with nilotinib that we previously described [4].We included in this study 82 chronic myeloid leukemia in chronic phase (CML-CP) patients treated frontline with nilotinib (42 patients, with the dose of 600 mg BID) or after failure of othe...

Comparative Assessment of Echocardiographic Patterns Among Chronic Myeloid Leukemia Patients on Tyrosine Kinase Inhibitor and Healthy Controls

“… 36 Improvement in oral intake may account for the significantly higher mean weight and BMI in the imatinib-treated CML group than in the imatinib-naive CML group. This observation is somewhat similar to the findings of Breccia et al, 37 who reported that 50% of CML patients treated with TKIs had a normal BMI. In addition, the release of cachexin and other cytokines can lead to weight loss in CML groups.…”

Challenges and Management of Acute Coronary Syndrome in Cancer Patients

“…In one larger retrospective study involving 81 patients receiving nilotinib, the incidence of AMI was 7.5% ( 23 ). In the analysis of 82 patients treated with nilotinib, the cumulative incidence of atherosclerotic events at 48 months was 8.5%, which was higher among patients with elevated cardiovascular risk ( 36 ). In a study that evaluated the effectiveness of ponatinib in the treatment of CML, treatment-related adverse cardiovascular events were observed in 2% ( 37 ).…”

Eurasian clinical guidelines for cardiovascular complications of cancer treatments: diagnosis, prevention and treatment (2022)

“…Высокий риск ишемических событий может сохраняться и после отмены препаратов, в том числе на фоне оптимальной терапии [194,195,196]. Перечисленные осложнения возможны при отсутствии у пациента факторов риска атеросклероза или сердечно-сосудистой патологии в анамнезе, однако при их наличии вероятность неблагоприятных событий возрастает [197]. В качестве возможных механизмов сосудистой токсичности рассматриваются подавление неоангиогенеза, дисфункция и гибель эндотелиальных клеток [198].…”