Treatment With Carfilzomib May Lead to Cardiovascular Toxicity in Patients With Multiple Myeloma

Key Points

  • 18.1% of patients who took carfilzomib experienced cardiovascular adverse events, with 8.2% of those cases being grade 3 or higher.
  • The most common cardiovascular adverse events were hypertension (12.2%) and heart failure (4.1%). Arrhythmias (2.4%) and ischemic events (1.8%) were observed less commonly.
  • Higher doses of carfilzomib are associated with higher rates of cardiovascular adverse events, and that carfilzomib was associated with an elevated risk of cardiovascular adverse events compared to control groups who did not receive carfilzomib.

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 multiple myeloma patients 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 Waxman et al in JAMA Oncology.

“Like any cancer therapy, the concern with this approach is that it may have an effect on an otherwise healthy part of the body—in this case, the heart,” said the study’s lead author Adam J. Waxman, MD, a Hematology Oncology fellow in the Perelman School of Medicine at the University of Pennsylvania.

Study Findings

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, another proteasome inhibitor, found just 3.8% of patients experienced cardiovascular adverse events, and only 2.3% of these effects were severe.

The most common cardiovascular adverse events were hypertension (12.2%) and heart failure (4.1%). Arrhythmias (2.4%) and ischemic events (1.8%) were observed less commonly.

Researchers also found that higher doses of carfilzomib are associated with higher rates of cardiovascular adverse events and that carfilzomib was associated with an elevated risk of these events compared to control groups who did not receive carfilzomib.

“Taken together, these findings argue that carfilzomib is responsible for an elevated risk, and anyone who is treating patients with this drug needs to be aware that this is a common event,” Dr. Waxman said.

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.

“Clinicians should be paying attention to who may be at highest risk for these events so they can tailor their therapy accordingly,” Dr. Waxman said.

Researchers also called for further clinical trials to specifically evaluate this connection, arguing that it may be underrepresented by current data.

“If you’re not specifically looking for this, you might report it differently,” Dr. Waxman concluded.

The study was supported by the National Institutes of Health (T32-GM075766).

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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