Carfilzomib Associated With Cardiotoxicity Risk in Multiple Myeloma

Cardiovascular adverse events (CVAEs) are more than twice as frequent in carfilzomib arms of randomized controlled trials and may go underdetected in phase I trials, according to a systematic review and meta-analysis of 24 studies of patients with multiple myeloma (abstract 8018) presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago.

“Carfilzomib CVAEs occurred in 18% and 8% of patients (all-grade and high-grade, respectively),” reported lead study author Adam Justin Waxman, MD, of the Abramson Cancer Center in Philadelphia, and colleagues. “Higher doses of carfilzomib are associated with more high-grade CVAEs (6.4% vs 11.9%).”

The most frequent of these were heart failure and hypertension, the team reported. Elevated rates of arrhythmia, ischemia, and cardiac arrest were all also associated with carfilzomib treatment (Ps < .001), the meta-analysis concluded.

Undifferentiated edema (affecting 25% of patients) and dyspnea (24%) were also frequent although it was not clear that these were always specific to CVAE, the authors cautioned.

The authors pooled data from five phase I, eight phase I/II, eight phase II, and three phase III clinical trials for analysis. The majority of the patients represented in the studies analyzed (n = 2,203) had relapsed/refractory multiple myeloma; 391 patients were newly diagnosed. Most (2,019) were age 60–65 years; 251 were 60 years old or younger at the time of trial participation and 324 were older than 65 years.

Researchers should seek to identify patients at high risk for CVAEs and to develop “optimal monitoring strategies,” as well as to evaluate treatments that might reduce the risk of CVAEs among patients with multiple myeloma, the authors concluded.