Cardiac events during treatment with proteasome inhibitor therapy for multiple myeloma

John H Chen; Daniel J Lenihan; Sharon E Phillips; Shelton L Harrell; Robert F Cornell

doi:10.1186/s40959-017-0023-9

Cardiac events during treatment with proteasome inhibitor therapy for multiple myeloma

Cardiooncology. 2017 Jun 1:3:4. doi: 10.1186/s40959-017-0023-9. eCollection 2017.

Authors

John H Chen¹, Daniel J Lenihan², Sharon E Phillips³, Shelton L Harrell¹, Robert F Cornell¹

Affiliations

¹ 1Department of Medicine, Division of Hematology-Oncology, Vanderbilt University Medical Center, 2220 Pierce Avenue, 777 PRB, Nashville, TN 37232 USA.
² 2Department of Medicine, Division of Cardio-Oncology, Vanderbilt Heart & Vascular Institute, 1215 21st Avenue South, 5209 MCE, Nashville, TN 37232 USA.
³ 3Department of Biostatistics, Division of Cancer Biostatistics, Vanderbilt University Medical Center, 2220 Pierce Avenue, 571 PRB, Nashville, TN 37232 USA.

Abstract

Background: Proteasome 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.

Methods: This 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.

Results: PI-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.

Conclusions: AEs 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.

Keywords: Bortezomib; Cardiotoxicity; Carfilzomib; Myeloma; Proteasome inhibitors; Risk factors.