Abstract 12978: Identification of Cardiovascular Adverse Effects Associated With Midostaurin - A WHO Pharmacovigilance Database Analysis

Abstract

Introduction: Midostaurin is an oral multiple tyrosine kinase inhibitor (TKI) approved for treatment of acute myeloid leukemia and systemic mastocytosis. Clinical trials have shown efficacy of midostaurin with few adverse events. Although midostaurin does cause QT-prolongation, other associated cardiovascular complications are unknown. The purpose of this study is to identify and characterize cardiovascular adverse events associated with midostaurin. Methods: We used VigiBase, WHO's global database of individual case safety reports, to evaluate the association between midostaurin and cardiovascular adverse events using the reporting odds ratio (ROR) and the information component (IC). IC is an indicator value for disproportionate Bayesian reporting that compares observed and expected values to find associations between drugs and adverse events. IC 025 is the lower end of the IC 95% credibility interval and an IC 025 value of more than zero is deemed significant. Results: We identified 153 adverse cardiovascular events reported in patients who received midostaurin. Midostaurin treatment was associated with higher reporting of QT prolongation (48 cases, IC 025 4.15), heart failure (38 cases, IC 025 1.90), atrial fibrillation (20 cases, IC 025 1.53), and pericardial disease (12 cases, IC 025 1.23). A majority of these adverse events occurred within 50 days of midostaurin initiation with midostaurin being the only suspected culprit medication. Fatalities occurred in 8.7%, 43.2%, and 42.1% of cases of QT prolongation, heart failure, and atrial fibrillation, respectively. Conclusions: Midostaurin can lead to severe and sometimes fatal cardiac toxicities in a subset of patients. Baseline electrocardiograms and echocardiograms would be prudent in patients starting midostaurin to characterize and monitor these adverse effects.