Evaluation of Cardiac Adverse Events Associated with Carfilzomib Using a Japanese Real-World Database

Background: Carfilzomib is a proteasome inhibitor widely used for the treatment of multiple myeloma. However, cardiac adverse events (CAEs) are a serious side effect of carfilzomib administration. Observational studies based on systematic reviews and real-world data have revealed that the risk of CAEs tends to be high. However, there have been no reports on the incidence of CAEs associated with carfilzomib in Japanese patients. Furthermore, there have been no reports on the timing and post-event outcomes of CAEs. Objectives: The purpose of this study was to identify the trends in carfilzomib-associated adverse events, the time to onset of CAEs, and the clinical outcomes after the occurrence of CAEs using the Japanese Adverse Drug Event Report (JADER) database. Method: We analyzed data from the JADER database, which contains reports of spontaneous adverse events submitted to the Pharmaceutical and Medical Device Agency, between April 2004 and December 2020. The relative risk of adverse events was estimated using the reporting odds ratio. The time to onset and post-event outcomes were evaluated for adverse cardiotoxic events with >10 reports. Results: The reporting rate was significantly higher for all 6 detected CAEs. A time-to-onset histogram of the 6 CAEs showed that they all occurred early after carfilzomib administration. The median time of onset of heart failure, congestive heart failure, and acute heart failure was approximately 2 weeks after treatment. The adverse events with the largest proportion of fatal clinical outcomes were acute heart failure (26%) and heart failure (9.5%). Conclusions: This study suggests that the early signs and symptoms of potential fatal heart failure should be monitored during carfilzomib treatment.