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

Abstract

PurposeCarfilzomib 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.MethodsWe 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.ResultsA 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.ConclusionThe 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.

Real‐world experience of carfilzomib‐associated cardiovascular adverse events: SEER‐Medicare data set analysis

“…Initially, carfilzomib associated CVAEs were reported in about 22% patients from the grouped data of four phase II studies in 2013 3 . Meta‐analyses of clinical trials have shown that up to 18% of patients experienced CVAEs 4–7 . These studies reported CVAEs with variable rates and the most common CVAEs were hypertension (18.5%) and heart failure (6.7%).…”

“…3 Meta-analyses of clinical trials have shown that up to 18% of patients experienced CVAEs. [4][5][6][7] These studies reported CVAEs with variable rates and the most common CVAEs were hypertension (18.5%) and heart failure (6.7%). Arrhythmia (2.4%) and ischemic events (3.7%) were observed less commonly.…”

Severe left atrial enlargement due to carfilzomib use in multiple myeloma

“…The authors concluded that carfilzomib use in relapsed or refractory myeloma patients significantly increases the risk of developing congestive heart failure but not ischemic heart disease. 6 Another meta-analysis by Waxman et al. 7 showed higher rates of cardiovascular toxicity with higher doses of carfilzomib at 45 mg/m 2 or higher.…”

“…A meta-analysis by Zhao et al. 6 included 2607 patients from eight prospective trials. The encountered cardiovascular adverse events were heart failure, hypertension, arrhythmias, and ischemia.…”

Mechanisms and Potential Treatment Options of Heart Failure in Patients With Multiple Myeloma

“…In a meta-analysis assessing carfilzomib, where 2,607 people with relapsed and refractory multiple myeloma (RRMM) were included, it was shown that all grade congestive heart failure developed in 5.5% of patients. This study concluded that carfilzomib in RRMM patients increased the risk of heart failure but not ischemic heart disease compared with control [ 15 ]. In phase three FOCUS trial where patients were randomly assigned to carfilzomib or low-dose corticosteroids with optional cyclophosphamide, it was shown that carfilzomib was associated with a higher prevalence of cardiac events, including cardiac failure (7% vs. 2%) [ 16 ].…”