Patterns of Cardiotoxicity Associated with Carfilzomib

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According to a new case series published in the Journal of Cardiac Failure, there was a common clinical syndrome of dyspnea with left ventricular systolic and/or diastolic dysfunction caused by carfilzomib, a proteasome inhibitor used for the treatment of multiple myeloma.

Despite the lack of clinical evidence that proteasome inhibitors result in heart failure in humans, studies with animal models and case reports with bortezomib, an older proteasome inhibitor than carfilzomib, have suggested that proteasome inhibitors do cause cardiotoxicity. In this case series, researchers describe six patients with relapsed or refractory multiple myeloma who experienced significant cardiotoxicity with carfilzomib. All patients experienced shortness of breath associated with left ventricular systolic and/or diastolic dysfunction.

The cardiotoxicity was mostly reversible when carfilzomib was discontinued immediately and medications that treat heart failure were initiated. For some patients, reinitiation of carfilzomib with dose modification was possible.

Carfilzomib (Kyprolis) was approved by the U.S. Food and Drug Administration in 2012 for the treatment of patients with multiple myeloma who have received at least two prior therapies, including bortezomib and an immunomodulatory agent.

Patients receiving carfilzomib should be monitored for cardiac complications and managed promptly. Patients with a history of cardiac abnormalities may be at greater risk for cardiac complications.

Patterns of Cadiotoxicity Associated With Carfilzomib
Common clinical syndrome of dyspnea with left ventricular systolic and/or diastolic dysfunction caused by carfilzomib.
Carfilzomib is a novel irreversible proteasome inhibitor (PI) used with increasing frequency to treat patients with relapsed and/or refractory multiple myeloma (RRMM). The authors describe the clinical presentation and management of six patients with RRMM who experienced significant cardiac toxicity associated with carfilzomib treatment.

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