PII-052 - PROTEOMIC ANALYSIS OF CARFILZOMIB (CFZ) RELATED HEART FAILURE IN MULTIPLE MYELOMA (MM) PATIENTS FROM PROSPECTIVE STUDY OF CARDIAC EVENTS DURING PROTEASOME INHIBITOR THERAPY (PROTECT) STUDY.

S. Shabnaz¹, R. Williams¹, S. Rubinstein², M. Fradley³, R. Baz⁴, C. Pepine¹, D. Lenihan⁵, R. Cornell⁶, Y. Gong¹; ¹University of Florida, Gainesville, FL, USA, ²University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, ³University of Pennsylvania, Philadelphia, PA, USA, ⁴H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA, ⁵Saint Francis Medical Center, Cape Girardeau, MO, USA, ⁶AbbVie Inc., Chicago, IL, USA.

Background: CFZ is efficacious in treating MM patients, but cardiovascular adverse events (CVAE) occur in 7.2- 22.7% of patients. Our previous metabolomics study discovered that patients who developed CVAE (including heart failure; HF) had lower levels of TUDCA than non-CVAE patients. TUDCA can prevent cardiomyocyte contractility by activating the PI3K/Akt/eNOS axis. This study aims to identify protein biomarkers that can differentiate patients at high risk of HF.

Methods: OLINK proteomics analysis was performed on the baseline (BL) and post-treatment (PT) plasma samples of 28 MM patients from PROTECT study including 14 HF patients and 14 age-, sex-matched non-HF patients (controls). T-test was performed on 368 proteins to identify proteins that are differentially expressed in HF vs controls. The proteins with p< 0.05 were included in LASSO Cox regression.

Results: Overall, 27 proteins were differentially expressed (with nominal significance) between the two groups at BL or PT. Beta-NGF was the only protein that was retained in the LASSO Cox regression model with a C-index of 0.83. In addition, HB EGF and IL17 were also differentially expressed in BL and PT (Table).

Conclusion: Our metabolomic and proteomic analyses identified biomarkers with different levels in HF vs controls which suggest the importance of PI3K/Akt/eNOS pathway in carfilzomib related HF.

Proteins differentially expressed at baseline and post-treatment.