Abstract
BackgroundProteasome inhibitors (PI) bortezomib and carfilzomib are cornerstone therapies for multiple myeloma. Higher incidence of cardiac adverse events (CAEs) has been reported in patients receiving carfilzomib. However, risk factors for cardiac toxicity remain unclear. Our objective was to evaluate the incidence of CAEs associated with PI and recognize risk factors for developing events.MethodsThis was a descriptive analysis of 96 patients with multiple myeloma who received bortezomib (n = 44) or carfilzomib (n = 52). We compared the cumulative incidence of CAEs using a log rank test. Patient-related characteristics were assessed and multivariate analysis was used to identify risk factors for developing CAEs.ResultsPI-related CAEs occurred in 21 (22%) patients. Bortezomib-associated CAEs occurred in 7 (16%) patients while carfilzomib-associated cardiac events occurred in 14 (27%) patients. The cumulative incidence of CAEs was not significantly different between agents. Events occurred after a median of 67.5 days on PI therapy. Heart failure was the most prevalent event type. More patients receiving carfilzomib were monitored by a cardiologist. By multivariate analysis, a history of prior cardiac events and longer duration of PI therapy were identified as independent risk factors for developing CAEs.ConclusionsAEs were common in patients receiving PIs. Choice of PI did not impact the cumulative incidence of CAEs. Early involvement by a cardiologist in patients at high risk for CAEs may help to mitigate the frequency and severity of CAEs.
Highlights
Proteasome inhibitors (PI) bortezomib and carfilzomib are cornerstone therapies for multiple myeloma
All patients in the carfilzomib cohort had prior exposure to bortezomib during previous lines of therapy; only bortezomib-related events in the bortezomib cohort and carfilzomib-related events in the carfilzomib cohort were included in the analysis
PI-related Cardiac adverse event (CAE) occurred in 22% (n = 21) of patients
Summary
Proteasome inhibitors (PI) bortezomib and carfilzomib are cornerstone therapies for multiple myeloma. Proteasome inhibitors (PIs) have become cornerstone therapies for management of MM [2,3,4,5,6] These agents bind to the constitutive 26S proteasome, causing accumulation of protein byproducts within plasma cells and subsequent apoptosis [7, 8]. Cardiac toxicities associated with carfilzomib identified in earlier studies include hypertension, arrhythmia, heart failure, ischemic heart disease and cardiomyopathy [9, 10]. These carfilzomib-associated toxicities were confirmed to occur at a higher incidence compared to bortezomib in the ENDEAVOR trial [11]. While a strong signal for cardiac toxicity has not been associated with bortezomib use, several case reports [12,13,14,15,16] have described CAEs in patients receiving this agent
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