Incidence and management of carfilzomib-induced cardiovascular toxici-ty; a systematic review and meta-analysis

Background: The ASPIRE and ENDEAVOUR trials have shown cardiovascular adverse effects in patients treated with carfilzomib-based regimens. Therefore, we conducted this me-ta-analysis of published clinical trials to identify the cumulative incidence and risk of cardiovascular adverse effects due to carfilzomib. Methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane library was per-formed, and we identified 45 prospective trials of carfilzomib with data on 5583 patients. Among all patients being treated with carfilzomib (N=5,583), 8.9% sustained all grade cardiotoxicity, while 4.4% sustained high-grade cardiotoxicity. All-grade hypertension was present in 13.2%, while the incidence of high-grade hypertension was 5.3%. Results: The observed incidences of all-grade heart failure, edema, and ischemia were 5.1%, 20.7%, and 4.6%, respectively. Likewise, for high-grade heart failure and edema observed incidence was 3.2%, and 2.7%, respectively. There was no difference in the event rate of all and high-grade cardiotoxicity between newly diagnosed multiple myeloma and relapsed/refractory (p-value 0.42 and 0.86, respectively). Likewise, we did not observe any difference in the event rate of all and high-grade cardiotoxicity when carfilzomib was used as a single agent versus when used in combination therapy with other agents (p-value 0.43 and 0.73, respectively). Conclusion: Carfilzomib is associated with a significant risk of cardiovascular toxicity and hyper-tension. With the increasing utilization of carfilzomib, it is critical for primary care physicians, on-cologists and cardiologists to be aware of the risk of cardiotoxicity associated with the use of carfil-zomib to recognize and treat baseline cardiovascular risk factors in such patients.