Cardiovascular effects of the addition of nilotinib to standard therapy for acute myeloid leukemia.

Abstract

e18505 Background: Angina, arrhythmias and QT prolongation have been cardiac adverse effects reported in clinical trials with nilotinib, which inhibits the tyrosine kinase activity of BCR-ABL and KIT. The objective of this study was to assess cardiac events in acute myeloid leukemia (AML) patients treated with standard therapy (an anthracycline plus cytarabine or 7+3) versus KIT positive AML patients treated with 7+3 plus nilotinib as part of a clinical trial. Methods: After IRB approval, 100 consecutive patients treated for newly diagnosed AML at Mayo Clinic who consented to the use of their medical records for research were identified and a retrospective chart review performed. The primary endpoint was heart failure defined by the modified Framingham criteria. Secondary endpoints included cancer therapeutics-related cardiac dysfunction (CTRCD) defined as a drop in ejection fraction of > 10% to < 53%, arrhythmias defined as a new rhythm abnormality other than sinus bradycardia or tachycardia resulting in a change to therapy or transfer to a higher level of care, and acute coronary syndromes (ACS) diagnosed by a cardiologist. Between group differences were assessed using t-tests, Wilcoxon tests, or Fisher’s exact tests. Results: Thirteen patients (13%) received nilotinib plus 7+3 and 87 patients (87%) received 7+3. No patients had a prior exposure to nilotinib. Median follow-up was 73 weeks (55-87) in the nilotinib plus 7+3 group and 83 weeks (30-139) in the 7+3 group. Groups were similar with respect to age, sex, comorbidities and baseline medical therapy. No significant difference was observed between those who did versus did not receive nilotinib respectively in the incidence of heart failure (8% vs. 14%), CTRCD (15% vs. 16%), ACS (0 vs. 3%) and arrhythmias (0 vs. 16%)(all p > 0.1). Conclusions: The addition of nilotinib to standard therapy for AML was not associated with an increase in cardiac events for at least 1 year of follow up. This finding is important as the use of tyrosine kinase inhibitors in combination with other chemotherapeutic agents may increase in the future with personalized medicine. However, the follow-up was insufficient to detect late onset cardiac toxicity and studies with longer follow-up are needed.