According to a study published in JAMA Oncology, carfilzomib significantly increases the rate of cardiovascular adverse events (CVAEs) in a dose-dependent manner among patients with multiple myeloma (MM).
CVAE occurrence is of particular concern among patients with MM as the 2 conditions share many risk factors; with the improvement of therapy and corresponding prolongation of survival, the intersection of these risk factors are only increasing. There have been an increasing number of carfilzomib-associated CVAE, but there is a paucity of data investigating the specific association with patients with MM.
For this meta-analysis and systematic review, investigators compiled phase 1 to 3 prospective clinical trials of carfilzomib therapy for patients with MM that had evaluable toxic effects data. Of the 514 assessed studies, 24 studies that had enrolled 2594 patients who received carfilzomib 15 mg/m2 to 88 mg/m2 were eligible for the review.
All-grade and grades 3 and higher CVAE were recorded, and included heart failure, ischemia, hypertension, and arrhythmia.
A total of 617 (18.1%) and 274 (8.2%) of all-grade and grades 3 and higher CVAE, respectively, were reported. Heart failure (4.1) and hypertension (12.2%) were the most frequently observed CVAE, and arrhythmias (2.4%) and ischemic events (1.8%) occurred less commonly.
The rates of CVAE was 2.3% and 9.5% in phase 1 compared with phase 2/3 studies (P = .02), and doses of carfilzomib smaller than 45 mg/m2 were associated with a lower rate of CVAE (6.4%), compared with doses higher than 45 mg/m2 (P = .02). Further analysis of phase 3 studies revealed that the relative risk was 1.8 and 2.2 for all-grade and grade 3 or higher CVAE, respectively, for patients in the carfilzomib arms compared with patients in the control arms.
Median age greater than 65 years, concurrent myeloma therapies, and prior myeloma therapies, were not found to be correlated with increased CVAE risk.
The authors concluded that “future studies are needed to identify patients at high risk for CVAE, develop optimal monitoring strategies, and explore strategies to mitigate these risks.”
Waxman AJ, Clasen S, Hwang WT, et al. Carfilzomib-associated cardiovascular adverse events [published online December 28, 2017]. JAMA Oncol. doi: 10.1001/jamaoncol.2017.4519