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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.

journal_name

J Card Fail

journal_title

Journal of cardiac failure

authors

Grandin EW,Ky B,Cornell RF,Carver J,Lenihan DJ

doi

10.1016/j.cardfail.2014.11.008

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

138-44

issue

2

eissn

1071-9164

issn

1532-8414

pii

S1071-9164(14)01307-4

journal_volume

21

pub_type

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