In a systematic review and meta-analysis reported in JAMA Oncology, Waxman et al found that any-grade and grade ≥ 3 cardiovascular adverse events occurred in 18.1% and 8.2% of patients receiving carfilzomib (Kyprolis) for multiple myeloma in clinical trials.
The study involved data from 24 studies including a total of 2,594 patients. Cardiovascular adverse events were defined as heart failure, hypertension, ischemia, and arrhythmia.
Any-grade and grade ≥ 3 cardiovascular events occurred in 617 (18.1%) and 274 (8.2%) patients, respectively. Higher-grade adverse events occurred in 2.3% of patients in phase I trials vs 9.5% of those in phase II or III trials (P = .02) and in 6.4% of patients receiving doses of < 45 mg/m2 vs 11.9% in those receiving ≥ 45mg/m2 (P = .02).
No association of risk for adverse events was observed for patients with a median age > 65 years, prior myeloma therapies, or concurrent myeloma therapies. In the 3 randomized trials included in the analysis, summary relative risks for cardiovascular adverse events were 1.8 for any grade and 2.2 for grade ≥ 3 in patients receiving carfilzomib vs patients not receiving carfilzomib.
The investigators concluded, “Carfilzomib was associated with a significant incidence of [cardiovascular adverse events], with higher rates seen with higher doses of carfilzomib. Phase 1 studies may be underdetecting [cardiovascular 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.”
Adam J. Waxman, MD, of the University of Pennsylvania, is the corresponding author for the JAMA Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.