Higher Rates of Cardiovascular Adverse Events in Patients With MM Treated With Carfilzomib

Carfilzomib is associated with a higher rate of cardiovascular adverse events (CVAE) in patients with multiple myeloma (MM), which highlights a need for increased awareness of these adverse events, according to a study published in JAMA Oncology.

CVAEs are important in MM because of the overlapping risk factors associated with MM and cardiovascular disease, such as older age and obesity, as well as a significant prevalence of coexisting cardiovascular disease in patients with MM, according to the authors of the study. Due to patients with MM living longer and the treatment landscape expanding, adverse event profiles are playing a larger role in providing personalized care.

"The nature and incidence of carfilzomib-associated CVAE is not currently known," wrote the authors. "Clinical trials performed in different patient populations and with varying treatment parameters have shown varying rates of CVAE."

The authors conducted a systematic review of studies cited in Medline from January 1, 2007, to January 1, 2017, searching for terms “carfilzomib,” “Kyprolis,” and “PX-171.” Data were independently extracted by 2 reviewers following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Pooled incident rates, relative risks, and 95% confidence intervals were determined using the random effects model.

The authors performed subgroup analyses to assess study-level characteristics associated with CVAE. CVAE events were defined as heart failure, hypertension, ischemia, and arrhythmia.

A total of 24 prospective studies consisting of 2594 patients were assessed. Results showed that the rate of all-grade CVAE ranged from 0% to 52%, and the rate of high-grade CVAE ranged from 0% to 45%. All-grade and grades 3 and higher CVAE were seen in 18.1% (617) and 8.2% (274) of patients, respectively. Heart failure (4.1%) and hypertension (12.2%) were the most common types of CVAE; arrhythmias (2.4%) and ischemic events (1.8%) were less common. There were 6 reported carfilzomib-associated cardiac arrests.

Both the phase of the trial and the dose of carfilzomib were linked with higher rates of high-grade CVAE; phase 1 trials had a rate of 2.3% compared with 9.5% for phase 2 and 3 trials (P =.02), and doses of carfilzomib less than 45 mg/m² had a rate of 6.4% compared to 11.9% for doses higher than 45 mg/m² (P =.02).

Longer infusion duration (30 minutes versus 10 minutes or less) showed a tendency towards higher rates of high-grade CVAE (11% versus 6.7%, P =.06); however, studies that had a 30-minute infusion length were also more likely to have a higher dose of carfilzomib (OR, 8.6; 95% Cl, 1.4-51.7; P =.02).

“It is critical that clinicians caring for patients with MM be aware of early signs of CVAE and promptly refer such patients for additional evaluation and to hold carfilzomib,” concluded the authors. “Further study is needed to assess patient-level risk factors to predict which patients are at highest risk of developing carfilzomib CVAE as well as to establish optimal monitoring strategies for patients receiving carfilzomib and to develop strategies to mitigate this risk.”

Reference

Waxman A, Clasen S, Hwang W, et al. Carfilzomib-associated cardiovascular adverse events. JAMA Oncol. 2017. doi:10.1001/jamaoncol.2017.4519. Published online ahead of print December 28, 2017.