Cardiotoxicity associated with carfilzomib: systematic review and meta-analysis. Issue 11 (2nd November 2018)

• Record Type: Journal Article
• Authors: Shah, Chintan; Bishnoi, Rohit; Jain, Ankur; Bejjanki, Harini; Xiong, Sican; Wang, Yu; Zou, Fei; Moreb, Jan S.
• Is Part Of: Leukemia & lymphoma. Volume 59:Issue 11(2018)
• Page Start: 2557
• Page End: 2569
• Publication Date: 2018-11-02
• Subjects: Carfilzomib -- kyprolis -- multiple myeloma -- toxicity -- cardiotoxicity; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.1080/10428194.2018.1437269
• Languages: English
• ISSNs: 1042-8194

Abstract

Abstract: Carfilzomib is a second-generation proteasome inhibitor (PI) that is approved for patients with relapsed or refractory multiple myeloma (RRMM) who failed ≥1 prior lines of therapy. We performed a systematic review of carfilzomib literature with meta-analysis to determine cumulative incidence of cardiotoxicity. After the literature search, we included a total of 29 eligible phase I/II, phase II and phase III clinical trials which used carfilzomib. The cumulative incidence and overall odds ratios (OR) were calculated with random effect model, using 'R' software with metaphor package. A total of 4164 patients with various malignancies were included. The overall estimated cumulative incidence of cardiotoxicity was 8.68% and 4.92%, respectively, for all-grade and high-grade (≥ grade 3) toxicity, which seems higher than other PIs. Compared to control group, the odds of developing cardiotoxicity due to carfilzomib was significantly higher with OR of 2.03 (95% CI: 1.19–3.46, p = .010) and 2.04 (95% CI: 1.31–3.17, p = .002) for all-grades and high grades, respectively. Concomitant immunomodulatory agents seem to increase the risk of cardiotoxicity (high-grade cardiotoxicity 6.45% and 4.34% with and without concomitant immunomodulatory agents, respectively ( p = .033)). There was no variation in the incidence of cardiotoxicity among newly diagnosed versus RRMM ( p = .38), and high versus standard dose carfilzomib ( p = .86).