Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials

Ajai Chari, A. Keith Stewart, Stuart D. Russell, Philippe Moreau, Joerg Herrmann, Jose Banchs, Roman Hajek, John Groarke, Alexander R. Lyon, George N. Batty, Sunhee Ro, Mei Huang, Karim S. Iskander, Daniel Lenihan

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Carfilzomib is a selective proteasome inhibitor approved for the treatment of relapsed and/or refractory multiple myeloma (RRMM). It has significantly improved outcomes, including overall survival (OS), and shown superiority vs standard treatment with lenalidomide plus dexamethasone and bortezomib plus dexamethasone. The incidence rate of cardiovascular (CV) events with carfilzomib treatment has varied across trials. This analysis evaluated phase 1-3 trials with .2000 RRMM patients exposed to carfilzomib to describe the incidence of CV adverse events (AEs). In addition, the individual CV safety data of .1000 patients enrolled in the carfilzomib arm of phase 3 studies were compared with the control arms to assess the benefit-risk profile of carfilzomib. Pooling data across carfilzomib trials, the CV AEs (grade $3) noted included hypertension (5.9%), dyspnea (4.5%), and cardiac failure (4.4%). Although patients receiving carfilzomib had a numeric increase in the rates of any-grade and grade $3 cardiac failure, dyspnea, and hypertension, the frequency of discontinuation or death due to these cardiac events was low and comparable between the carfilzomib and control arms. Serial echocardiography in a blinded cardiac substudy showed no objective evidence of cardiac dysfunction in the carfilzomib and control arms. Moreover, carfilzomib had no significant effect on cardiac repolarization. Our results, including the OS benefit, showed that the benefit of carfilzomib treatment in terms of reducing progression or death outweighed the risk for developing cardiac failure or hypertension in most patients. Appropriate carfilzomib administration and risk factor management are recommended for elderly patients and patients with underlying risk factors.

Original languageEnglish (US)
Pages (from-to)1633-1644
Number of pages12
JournalBlood Advances
Volume2
Issue number13
DOIs
StatePublished - Jul 10 2018

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Multiple Myeloma
Clinical Trials
Safety
Heart Failure
Hypertension
Dyspnea
Dexamethasone
carfilzomib
Proteasome Inhibitors
Survival
Incidence
Risk Management
Therapeutics
Echocardiography
Meta-Analysis

ASJC Scopus subject areas

  • Hematology

Cite this

Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials. / Chari, Ajai; Keith Stewart, A.; Russell, Stuart D.; Moreau, Philippe; Herrmann, Joerg; Banchs, Jose; Hajek, Roman; Groarke, John; Lyon, Alexander R.; Batty, George N.; Ro, Sunhee; Huang, Mei; Iskander, Karim S.; Lenihan, Daniel.

In: Blood Advances, Vol. 2, No. 13, 10.07.2018, p. 1633-1644.

Research output: Contribution to journalArticle

Chari, A, Keith Stewart, A, Russell, SD, Moreau, P, Herrmann, J, Banchs, J, Hajek, R, Groarke, J, Lyon, AR, Batty, GN, Ro, S, Huang, M, Iskander, KS & Lenihan, D 2018, 'Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials', Blood Advances, vol. 2, no. 13, pp. 1633-1644. https://doi.org/10.1182/bloodadvances.2017015545
Chari, Ajai ; Keith Stewart, A. ; Russell, Stuart D. ; Moreau, Philippe ; Herrmann, Joerg ; Banchs, Jose ; Hajek, Roman ; Groarke, John ; Lyon, Alexander R. ; Batty, George N. ; Ro, Sunhee ; Huang, Mei ; Iskander, Karim S. ; Lenihan, Daniel. / Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials. In: Blood Advances. 2018 ; Vol. 2, No. 13. pp. 1633-1644.
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