Cardiovascular Safety of Carfilzomib in Patients with Multiple Myeloma

Proteasome inhibitors (PIs), comprising the first-generation agent bortezomib and the second-generation agents carfilzomib and ixazomib are key therapies for multiple myeloma (MM). This study evaluated the cardiovascular (CV) safety of carfilzomib by comparing outcomes with other PIs in a real-world, propensity score-matched (PSM) cohort.

A retrospective cohort study was conducted using the TriNetX global health research network. Adults with MM treated with carfilzomib or other PIs were identified, and 1:1 PSM was applied to create balanced cohorts. Outcomes included heart failure (HF), hypertension, atrial fibrillation (AF), myocardial infarction (MI), and stroke, as well as a composite endpoint of all-cause mortality, MI, or stroke (all-cause 3P-MACE).

After PSM, 7776 patients were included in each cohort. The mean age was 70.6 ± 10.6 years in the carfilzomib cohort and 71.1 ± 11.0 years in the non-carfilzomib cohort. The risk of HF (Hazard ratios, HR [95% confidence intervals, 95% CI], 1.40 [1.27-1.55], P = .831), AF (HR [95% CI], 1.08 [0.96-1.20], P = .316), hypertension (HR [95% CI], 1.37 [1.23-1.52], P = .579), MI (338 vs. 368 patients; HR [95% CI], 1.10 [0.95-1.28], P = .719), and stroke (234 vs. 247 patients; HR [95% CI], 1.16 [0.96-1.38], P = .367) did not differ between groups. However, carfilzomib was associated with a significantly increased risk of the all-cause 3P-MACE (HR [95% CI], 1.67 [1.58-1.77], P = .014).

In this large real-world PSM analysis, carfilzomib was not associated with an increased risk of individual CV outcomes compared with other PIs, but it was linked to a higher incidence of all-cause 3P-MACE, underscoring the need for careful CV monitoring.