Background: The ASPIRE and ENDEAVOUR trials have shown cardiovascular adverse
effects in patients treated with carfilzomib-based regimens. Therefore, we conducted this meta-
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 performed,
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 highgrade
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 hypertension.
With the increasing utilization of carfilzomib, it is critical for primary care physicians, oncologists
and cardiologists to be aware of the risk of cardiotoxicity associated with the use of carfilzomib
to recognize and treat baseline cardiovascular risk factors in such patients.