# Differential Expression of Circulating miRNAs and Carfilzomib-Related Cardiovascular Adverse Events in Patients with Multiple Myeloma

## TL;DR

This study finds that certain microRNAs in the blood may predict cardiovascular side effects in multiple myeloma patients treated with carfilzomib.

## Contribution

The study identifies specific miRNAs associated with carfilzomib-related cardiovascular adverse events in multiple myeloma patients.

## Key findings

- 13 miRNAs were differentially expressed at baseline in patients who developed cardiovascular adverse events.
- Three miRNAs showed differential expression post-treatment in patients with and without cardiovascular adverse events.
- Five miRNAs responded differently to carfilzomib treatment in patients with and without cardiovascular adverse events.

## Abstract

This study investigates the association between circulating microRNA (miRNA) expression and cardiovascular adverse events (CVAE) in multiple myeloma (MM) patients treated with a carfilzomib (CFZ)-based regimen. A cohort of 60 MM patients from the Prospective Observation of Cardiac Safety with Proteasome Inhibitor (PROTECT) study was analyzed. Among these, 31 patients (51.6%) developed CVAE post-CFZ treatment. The Taqman OpenArray Human microRNA panels were used for miRNA profiling. We identified 13 differentially expressed miRNAs at baseline, with higher expressions of miR-125a-5p, miR-15a-5p, miR-18a-3p, and miR-152-3p and lower expression of miR-140-3p in patients who later developed CVAE compared to those free of CVAE, adjusting for age, gender, race, and higher B-type natriuretic peptide levels. We also identified three miRNAs, including miR-150-5p, that were differentially expressed in patients with and without CVAE post-treatment. Additionally, five miRNAs responded differently to CFZ treatment in CVAE vs. non-CVAE patients, including significantly elevated post-treatment expression of miR-140-3p and lower expressions of miR-598, miR-152, miR-21, and miR-323a in CVAE patients. Pathway enrichment analysis highlighted the involvement of these miRNAs in cardiovascular diseases and vascular processes. These findings suggest that specific miRNAs could serve as predictive biomarkers for CVAE and provide insights into the underlying mechanisms of CFZ-CVAE. Further investigation is warranted before these findings can be applied in clinical settings.