Cardiovascular Adverse Events and Multiple Myeloma Treatment
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.
Study Details
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.
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