PII-049 - MIRNA-125A ASSOCIATION WITH CARFILZOMIB-RELATED CARDIOVASCULAR ADVERSE EVENTS IN MULTIPLE MYELOMA PATIENTS: PROSPECTIVE OBSERVATION OF CARDIAC SAFETY WITH PROTEASOME INHIBITOR (PROTECT) STUDY.
Thursday, March 23, 2023
5:00 PM – 6:30 PM EDT
M. Tantawy1, T. Langaee1, D. Wang1, S. Rubinstein2, R. Cornell3, D. Lenihan4, M. Fradley5, Y. Gong1; 1University of Florida, Gainesville, FL, USA, 2University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 3AbbVie Inc., Chicago, IL, USA, 4Saint Francis Medical Center, Cape Girardeau, MO, USA, 5University of Pennsylvania, Philadelphia, PA, USA.
Post Doctoral Associate University of Florida Gainesville, Florida, United States
Background: Carfilzomib (CFZ) is a proteasome inhibitor used in Multiple Myeloma (MM) patients and is associated with cardiovascular adverse events (CVAE). microRNAs (miRNAs) regulate gene expression at the posttranscriptional level through binding to target mRNA. Our study aimed to identify circulating miRNA in plasma as a potential biomarker and explore the CFZ-related CVAE (CFZ-CVAE) mechanism. Methods: Circulating miRNAs were profiled in the baseline and post-treatment (Six- month visit for non-CVAE patients, and at the CVAE visit for CVAE patients) in plasma samples of MM patients from the PROTECT study using TaqMan OpenArray Human MicroRNA panels (~750 of miRNAs). We performed logistic regression adjusted for age, gender, Brain-natriuretic peptide (BNP), and ancestry, for baseline and after treatment. Results: A total of 60 patients (31 patients with CFZ-CVAE) were included in this study. The Relative expression level of miR-125a was significantly higher in the CVAE patients than in the non-CVAE patients at baseline. The odds ratio (OR) and 95% confidence interval (CI) were 1.25 (1.05-1.48) (P = 0.014, fold-change [FC] =12.9). However, this miRNA was not significantly changed in post-treatment patients, the OR and 95% CI were 1.12 (0.96-1.32) (P=0.15, FC= 3.87). The changes in the expression of miR-125a before and after treatment was also not significantly different between CVAE and non-CVAE patients (P=0.55). It was reported that this miRNA is upregulated in the plasma of humans, and cardiac cells in rats with heart failure and acute ischemic stroke. Conclusion: Elevated circulating miR-125a at baseline may be a biomarker for CFZ-CVAE. Further study in larger sample size is warranted.
