A recent study found over 18% of patients with relapsed or refractory multiple myeloma treated with a proteasome inhibitor were faced with cardiovascular adverse events, published in JAMA Oncology (online December 28, 2017; doi:10.1001/jamaoncol.2017.4519).
Cardiovascular adverse events resulting from treatment with carfilzomib in patients with multiple myeloma have the potential to be life-threatening. However, the rate of such events among this population has yet to be fully understood.
Adam J Waxman, MD, division of hematology and oncology, Abramson Cancer Center, University of Pennsylvania, and colleagues conducted the first systematic review and meta-analysis of carfilzomib-associated cardiovascular adverse events. Researchers searched PubMed, EMBASE, Web of Science, and clinicaltrials.gov to identify phase I-III prospective clinical trials, with the intent to determine the incidence of carfilzomib-associated cardiovascular adverse events and to compare the rates of these adverse events among different doses and companion therapies.
Cardiovascular adverse events were predefined as heart failure, hypertension, ischemia, and arrhythmia. Researchers included all-grade and grades 3 or higher adverse events.
After narrowing their search to 24 studies and a total of 2594 patients, researchers reported all-grade and grade 3 or higher cardiovascular adverse events were observed in 18.1% (n = 617) and 8.2% (n = 274) of patients, respectively.
Subgroup analyses revealed that phase II-III studies and carfilzomib doses of 45 mg/m2 or higher were associated with high-grade cardiovascular events. Contrarily, median age older than 65 years, prior multiple myeloma therapies, and concurrent multiple myeloma therapies were not associated with cardiovascular adverse events.
Dr Waxman and colleagues concluded that carfilzomib is associated with a significant incidence of cardiovascular adverse events, with higher doses of carfilzomib correlating with higher rates of adverse events. “Future studies are needed to identify patients at high risk for cardiovascular adverse events, develop optimal monitoring strategies, and explore strategies to mitigate these risks,” researchers wrote, adding that phase I studies may be under-detecting cardiovascular adverse events.—Zachary Bessette