The proteasome inhibitor carfilzomib (Kyprolis) has taken on an increasing role in the treatment of multiple myeloma, but new research from the Abramson Cancer Center of the University of Pennsylvania shows the therapy may come with the risk of cardiovascular problems in a higher-than-expected percentage of patients. An analysis of past studies shows 18% of patients with multiple myeloma receiving carfilzomib experience cardiovascular adverse events such as hypertension, heart failure, heart attacks, or arrhythmia. More than 8% of patients experience high-grade cardiovascular adverse events that are more severe, which is more than twice as common as with other drugs for treating relapsed myeloma. These findings were published by Adam J. Waxman, MD, a hematology oncology fellow in the Perelman School of Medicine at the University of Pennsylvania, and colleagues in JAMA Oncology.
Researchers gathered data from 24 studies reported from 2007 through 2017, which included information on 2,594 patients with multiple myeloma. They found 18.1% of patients who took carfilzomib experienced cardiovascular adverse events, with 8.2% of those cases being grade 3 or higher. For comparison, a similar review of bortezomib (Velcade), another proteasome inhibitor, found 3.8% of patients experienced cardiovascular adverse events, and 2.3% of these effects were severe.
The most common cardiovascular adverse events were hypertension (12.2%) and heart failure (4.1%). Arrhythmia (2.4%) and ischemic events (1.8%) were observed less commonly. Higher doses of carfilzomib seem to be associated with higher rates of cardiovascular adverse events and that carfilzomib was associated with an elevated risk of these events compared with control groups who did not receive carfilzomib.
Researchers say these findings are particularly important, since there are already overlapping risk factors for both multiple myeloma and cardiovascular disease, such as older age and obesity. Previous studies have shown nearly two-thirds of patients with multiple myeloma had cardiovascular disease at baseline, and 70% experienced cardiovascular events within 6 years. In addition, further clinical trials are needed to specifically evaluate this connection, as it may be underrepresented by current data, they noted. ■