Qtc interval prolongation during targeted therapy with tyrosine kinase inhibitors for patients with chronic myeloid leukemia

Abstract

Background The advances in the treatment of chronic myeloid leukemia using tyrosine kinase inhibitors have led to unequivocal improvement in the survival of those patients. However, the effect of tyrosine kinase inhibitors on cardiac repolarization causing QT interval prolongation and the potential risk of life-threatening arrhythmia Torsade de pointes poses a challenging risk.Objective The objective of this study was to assess the prevalence of QTc interval prolongation in patients with chronic myeloid leukemia receiving imatinib or nilotinib therapy.Patients and methods A total of 43 patients were included in this cross-sectional study, where 22 patients were on nilotinib and 21 patients were on imatinib. Electrocardiogram was done for patients while on tyrosine kinase inhibitors (TKI) therapy. Corrected QTc interval was assessed using Bazett’s formula.Results The prevalence of QTc prolongation in the total cohort of patients was 46.5%. Moreover, 23.3% of patients had QTc more than or equal to 500 ms. The mean QTc in patients receiving imatinib was 467 ms, whereas the mean QTc in patients on nilotinib was 433.5 ms, with a statistically significant difference (P=0.033). Overall, 61.9% of patients on imatinib had prolonged QTc compared with 31.8% of patients on nilotinib, with a statistically significant difference (P=0.048). However, although nonstatistically significant, the median QTc percentage prolongation for patients on nilotinib is 10.8 compared with 5.1 for patients on imatinib. No statistically significant sex difference was found; however, the mean QTc was higher in females (455.93 ms) compared with males (439.69 ms) (P=0.327). No significant difference was found between QTc and duration of TKI use or correlation between QTc and age.Conclusion The prevalence of QTc prolongation is significantly increased in patients with chronic myeloid leukemia (CML) treated with either imatinib or nilotinib. ECG monitoring in those patients is strongly recommended to prevent life-threatening arrhythmias.