Usefulness of a new risk score in identifying patients with CML at increased risk of cardiovascular toxicities

Abstract

Abstract Background Anti-BCR-ABL tyrosine kinase inhibitors (TKIs) dramatically improved the prognosis of patients with Chronic Myeloid Leukemia (CML) however they have been associated with cardiovascular (CV) complications. Purpose The primary aim of our study was to compare the usefulness of two different tools to stratify the risk of developing cardiovascular adverse events in haematology patients treated with ponatinib or nilotinib. Methods A real-life retrospective observational study was carried out on 58 patients (32 M, 26 W; mean age ± SD: 59±15) affected by CML treated with TKIs for a median period of 43±31 months. Patients were divided in groups according to CV risk estimated with SCORE and the 2020 CV risk assessment proposed by the Cardio-Oncology Study Group of the ESC/ICOS. Cardiac evaluation and echocardiogram were performed in all patients. The recorded CV adverse events were: myocardial ischemia, peripheral vascular diseases, new-onset or progression of preexisting carotid atherosclerosis, arterial hypertension, arrhythmias. Results According to SCORE, 46% of patients were at high-very high risk (group A1) and 54% at low-moderate risk (group B1). Applying the ESC/ICOS risk stratification tools, 60% were at high-very high risk (group A2) and 40% at low-medium risk (group B2). 21 CV adverse events were observed. CV adverse events were significantly more frequent in group A1 than group B1 (p value = 0,0003) when considered overall, they were significantly more frequent in group A2 than group B2 either overall (p=0,0004) or considered individually (myocardial ischemia: p=0,01; peripheral arterial disease: p=0,03). See Table 1. Moreover, the ESC/ICOS risk stratification tools was significantly more sensitive than SCORE (p=0,0004) in identifying patients at higher risk of cardiovascular toxicity. See Table 2. No patients treated with Ponatinib showed CV adverse events during follow up. It is worth of notice that all patients before starting treatment underwent cardio-oncological evaluation, risk factors correction and preventive treatment with aspirin. They also were treated with the lowest dose of TKI. None of the patients treated with nilotinib over 4 years and with multiple lines of therapy, experiencing adverse events, received aspirin in primary prevention. Conclusions Our study shows that the ESC/ICOS risk stratification tools is very sensitive and more performing than SCORE for risk stratification of cardiotoxicity in haematology patients treated with TKIs. It also suggests that baseline CV risk assessment, CV risk factors correction and preventive treatment with aspirin aid in reducing CV adverse events in patients treated with ponatinib. Funding Acknowledgement Type of funding sources: None. Table 1Table 2