Development of cardiovascular toxicity in patients with chronic myeloid leukemia treated with the second-generation tyrosine kinase inhibitor bozutinib

Tyrosine kinase inhibitors have a beneficial effect on the prognosis and life expectancy of patients with chronic myeloid leukemia. At the same time, some of them have a negative effect on the cardiovascular system. The study of left ventricular contractility based on longitudinal deformation is currently the most informative method for displaying myocardial function.

The purpose of the study. To analyze the indicators affecting the development of cardiotoxicity in patients with chronic myeloid leukemia undergoing therapy with bosutinib at a daily dosage of 500 mg.

Materials and methods of research. The study included 47 people (30 men (63.8%)/17 women (36.2%) with a diagnosis of chronic myeloid leukemia before starting bosutinib therapy were selected for the study. All patients underwent a study of standard clinical, laboratory, and instrumental parameters, as well as transthoracic echocardiography to determine the global longitudinal deformation of the left ventricle. 

Results. By 12 months, 6 (12.8%) patients had progressed to stage 2 hypertension, and 2 (4.25%) patients (p=0.112) developed stable angina pectoris of FC I and CHF of FC I (NYHA). An increase in total cholesterol levels (4.9 (4.36;5.31) mmol/L before therapy vs. 4.91 (4.2;5.46) mmol/L, <0.001) by 12 months of therapy and LDL-C (2.31 (1.76;3.04) mmol/L before therapy vs. 2.3 (1.72;2.58) mmol/L, p=0.009) by 6 months. By month 12, all patients showed an increase in size (CDR 50.0 (46.0;51.0) and CDR 31.5 (30.0;34.0) before therapy versus 53.0 (49.0;54.0) and  33.5 (32.0;36.0), p<0.001) and volume of the left ventricle (CDR 111.0 (97.0;127.75) and CSR 57.0 (51.0;59.0) before therapy versus 116.5 (98.75; 130.0) and 58.0 (53.0;61.75), p<0.001). A decrease in left ventricular ejection fraction by 12 months (60.0 (59.0;62.0) before therapy vs 59.0 (57.25;60.0), p<0.001) was considered a sign of systolic dysfunction. By month 12, 5/47 (10.64%) showed a decrease in global longitudinal deformity of 21.5(18.6;21.6) before therapy versus 14.5(14.2;14.7), p<0.001).

Conclusion. The analysis of the set of indicators allows us to speak about the development of cardiotoxicity in 5/47 (10.64%) of patients with chronic myeloid leukemia who are on bosutinib therapy, which is confirmed by the detected decrease in global longitudinal deformation of the left ventricle. These data should be interpreted as necessary for further monitoring and timely correction.

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