Myeloma: Proteasome Inhibitors and IMiDs May Increase Risk of Cardiovascular Complications

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Patients with underlying cardiovascular disease and/or baseline hypertension and coronary artery disease may be at a higher risk.
Patients with underlying cardiovascular disease and/or baseline hypertension and coronary artery disease may be at a higher risk.

Although proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) have dramatically improved outcomes for patients with multiple myeloma, the combination may increase the risk of cardiac toxicity, according to a newly published report.1

Various combinations of PIs, such as bortezomib, carfilzomib, and ixazomib, and IMiDs like lenalidomide, pomalidomide, and thalidomide, are co-administered in conjunction with dexamethasone as front-line therapy and in previously treated disease.

The phase 3 ENDEAVOR trial (ClinicalTrials.gov Identifier: NCT01568866) evaluated the efficacy and safety of carfilzomib plus dexamethasone vs bortezomib plus dexamethasone in 929 patients with relapsed or refractory multiple myeloma. One-fourth carfilzomib-treated patients had hypertension and 9% had grade 3 or worse cardiovascular events — compared with only 3% in the in the bortezomib arm.2 A pooled analysis of 4 phase 2 studies also showed cardiotoxicity in more than 20% of patients treated with carfilzomib.3

In a long-term safety analysis of 2 phase 3 trials, researchers observed thromboembolic events in 15.9% of patients treated with lenalidomide plus dexamethasone vs 5.4% of patients who received dexamethasone alone.4

In clinical practice, however, patients often receive PIs and IMiDs as part of a triplet therapy with dexamethasone. A phase 3 study of 781 patients with relapsed myeloma showed that patients treated with carfilzomib, lenalidomide, and dexamethasone (KRd) had higher rates of cardiovascular complications including heart failure, ischemic heart disease, hypertension, and venous thromboembolism compared with patients treated with lenalidomide plus dexamethasone.5

“It is important that oncologists, cardiologists, and cardio-oncologists are aware of the potential cardiotoxicities associated with novel multiple myeloma treatments so as to better monitor and treat these patients,” said lead author Michael G. Fradley, MD, of the Moffitt Cancer Center in Tampa, Florida, in an interview with Cancer Therapy Advisor. “With increased recognition, we can develop better risk mitigation strategies to ensure patients can continue to receive optimal care for their cancer while minimizing the likelihood of cardiovascular disease.”

Dr Fradley explained that although researchers have yet to determine the risk factors most associated with cardiotoxicity, it appears that patients with underlying cardiovascular disease and/or baseline hypertension and coronary artery disease are likely at a higher risk.

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