Incidence and risk of cardiac toxicities in patients with relapsed and refractory multiple myeloma treated with carfilzomib

Purpose: Carfilzomib has been approved for use in relapsed and refractory multiple myeloma (RRMM). Cardiac toxicities have been reported with the use of carfilzomib. We aimed to determine the overall incidence and risk of cardiac toxicities in RRMM patients treated with carfilzomib using a meta-analysis.

Methods: We searched several databases for relevant articles. Prospective trials evaluating carfilzomib in RRMM patients with adequate data on cardiac toxicities were included for analysis. Pooled incidence, Peto ORs, and 95% CIs were calculated according to the heterogeneity of selected studies.

Results: A total of 2,607 RRMM patients from eight prospective trials were included. The pooled incidence of all-grade congestive heart failure (CHF) and ischemic heart disease (IHD) related to carfilzomib in RRMM patients was 5.5% (95% CI: 4.3%-6.9%) and 2.7% (95% CI: 1.1%-6.7%), respectively. In addition, the use of carfilzomib significantly increased all-grade (Peto OR 2.33, 95% CI: 1.56-3.48, p<0.001) and high-grade (Peto OR 3.22, 95% CI: 1.84-5.61, p<0.001) CHF when compared to controls, whereas there was no significantly increased risk of developing all-grade (Peto OR 1.31, 95% CI: 0.79-2.18, p=0.30) and high-grade (Peto OR 1.41, 95% CI: 0.73-2.72, p=0.31) IHD in RRMM patients receiving carfilzomib.

Conclusion: The use of carfilzomib in RRMM patients significantly increases the risk of developing CHF but not IHD. Clinicians should be cautious about the risk of CHF associated with carfilzomib to maximize the benefits and minimize the toxicities.