Clinical InvestigationPatterns of Cardiac Toxicity Associated With Irreversible Proteasome Inhibition in the Treatment of Multiple Myeloma
Section snippets
Patient 1
A 59-year-old Haitian woman with hypertension was treated for IgG kappa multiple myeloma for ∼10 years with the use of combinations of dexamethasone, melphalan, thalidomide, lenalidomide, and bortezomib. In February 2013 she started carfilzomib and dexamethasone for RRMM. A baseline 2-dimensional transthoracic echocardiogram (2D-echo) showed normal left ventricular (LV) systolic function (Table 1). Three months later, she presented with New York Heart Association (NYHA) functional class III HF
Discussion
Cardiovascular toxicity is a significant concern with carfilzomib, but it remains poorly understood. Initial trials and pooled safety data suggested an incidence of HF of ∼7%, but more recent reports note a higher incidence of up to 11% with higher drug doses.19 Cases of HF have been observed across multiple tumor types,20 and dyspnea is one of the most commonly reported symptoms but usually with few clinical details to interpret etiology. In the present case series, we describe a spectrum of
Study Limitations
Several limitations of this case series are noted. We were not able to define the overall incidence of cardiac dysfunction with this agent; that is better accomplished through prospective cohort studies or retrospective analyses of large clinical trial databases. During the time period in which these cases occurred, there were 25 patients treated with carfilzomib at Vanderbilt and 20 patients treated at Penn resulting in crude incidence rates of cardiac toxicity of 12% and 15%, respectively.
Conclusion
This case series highlights the potential risk of substantial cardiac toxicity in patients with RRMM being treated with carfilzomib. Our findings suggest that all patients should have a comprehensive cardiovascular evaluation before initiating PI therapy, and the development of new dyspnea during therapy warrants expedient evaluation for cardiotoxicity. There is a common clinical syndrome of dyspnea with LV systolic and diastolic dysfunction, although there is a wide range in the severity of
Disclosures
Dr Lenihan is a consultant for Onyx Pharmaceuticals, which manufactures carfilzomib. The other authors report no other relevant conflicts of interest regarding this manuscript.
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