Carfilzomib appeared linked with cardiovascular adverse events among patients receiving the drug for multiple myeloma, suggesting that phase 1 studies may under-detect such events, a systematic review and meta-analysis found.
“Cardiovascular adverse events are particularly important in multiple myeloma given the overlapping risk factors for both multiple myeloma and cardiovascular disease, such as older age and obesity, as well as a significant prevalence of coexisting cardiovascular disease [among] patients with multiple myeloma,” Adam J. Waxman, MD, of the University of Pennsylvania, and colleagues wrote.
Recent reports have suggested instances of carfilzomib-associated cardiovascular adverse events, the researchers noted, such as severe hypertension, heart failure, cardiac arrhythmias, ischemic events and cardiac arrest.
“The nature and incidence of carfilzomib-associated cardiovascular adverse events is not currently known,” Waxman and colleagues wrote.
The researchers performed a systematic review and meta-analysis using PubMed, EMBASE and Web of Science databases. They evaluated a total of 24 phase 1 to phase 3 clinical trials of carfilzomib, which included 2,594 patients with multiple myeloma. Waxman and colleagues calculated pooled incidence rates and relative risks with a random effects model, and performed subgroup analyses for study-level characteristics associated with cardiovascular events.
Cardiovascular adverse events occurred in 617 patients (18.1%) across the studies, with 274 (8.2%) events of grade 3 or higher. The severity of events appeared to be linked with carfilzomib doses of 45 mg/m2 or higher. Phase 2 and phase 3 studies also appeared to be associated with higher-grade cardiovascular adverse events.
However, prior myeloma therapies, concurrent therapies and median age older than 65 years did not show an association with cardiovascular adverse events.
The study sample included three randomized clinical trials. In these trials, the summary relative risk for all-grade cardiovascular adverse events among patients treated with carfilzomib compared with other drugs was 1.8 and for grade 3 or higher events was 2.2.
“It is critical that clinicians caring for patients with multiple myeloma be aware of early signs of cardiovascular adverse events and promptly refer such patients for additional evaluation and to hold carfilzomib,” the researchers wrote. – by Andy Polhamus
Disclosures: Waxman reports training grants from the NIH. No other authors report any relevant financial disclosures.