title: Patterns of cardiac toxicity associated with irreversible proteasome inhibition in the treatment of multiple myeloma.
abstract: Carfilzomib is a novel irreversible proteasome inhibitor (PI) used with increasing frequency to treat patients with relapsed and/or refractory multiple myeloma (RRMM). This agent is an effective treatment for this challenging population, but proteasome inhibition has the potential of significant cardiac toxicity via the accumulation of intracellular protein aggregates. Although large clinical trials have not suggested an excess of heart failure with PI therapy, nonhuman animal studies and case reports in humans with the PI bortezomib have suggested otherwise. We describe the clinical presentation and management of 6 patients with RRMM who experienced significant cardiac toxicity associated with carfilzomib treatment. A common clinical syndrome of dyspnea associated with left ventricular systolic and/or diastolic dysfunction was identified. These abnormalities were largely reversible with prompt cessation of PI therapy and initiation of traditional heart failure treatments. Safe readministration of carfilzomib with dose modification was possible in some cases.
authors.affiliation: Department of Medicine, Division of Cardiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: E Wilson
authors.initials: EW
authors.lastname: Grandin
authors.affiliation: Department of Medicine, Division of Cardiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Ky
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Vanderbilt University, Nashville, Tennessee.
authors.forename: R Frank
authors.initials: RF
authors.lastname: Cornell
authors.affiliation: Department of Medicine, Division of Cardiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Joseph
authors.initials: J
authors.lastname: Carver
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University, Nashville, Tennessee. Electronic address: daniel.lenihan@vanderbilt.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lenihan
mesh_terms: D000368:Aged; D066126:Cardiotoxicity / Q000150:complications / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D009842:Oligopeptides / Q000009:adverse effects*; D061988:Proteasome Inhibitors / Q000009:adverse effects*; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D009842:Oligopeptides; D061988:Proteasome Inhibitors; C524865:carfilzomib
keywords: Carfilzomib; chemotherapy; heart failure; proteasome inhibitor