Metabolomic signatures of carfilzomib‐related cardiotoxicity in patients with multiple myeloma

Author:

Shabnaz Samia1ORCID,Nguyen Trang N.1ORCID,Williams Roy1ORCID,Rubinstein Samuel M.2ORCID,Garrett Timothy J.3ORCID,Tantawy Marwa1ORCID,Fradley Michael G.4,Alomar Mohammed E.5ORCID,Shain Kenneth H.5ORCID,Baz Rachid C.5ORCID,Lenihan Daniel6,Cornell Robert F.7ORCID,Lu Qing8ORCID,Gong Yan19ORCID

Affiliation:

1. Department of Pharmacotherapy and Translational Research Center for Pharmacogenomics and Precision Medicine, College of Pharmacy University of Florida Gainesville Florida USA

2. Department of Medicine, Division of Hematology University of North Carolina Chapel Hill North Carolina USA

3. Department of Pathology, Immunology and Laboratory Medicine, College of Medicine University of Florida Gainesville Florida USA

4. Cardio‐Oncology Center of Excellence, Division of Cardiology, Department of Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA

5. Department of Malignant Hematology H. Lee Moffitt Cancer Center & Research Institute Tampa Florida USA

6. Cape Cardiology Group Saint Francis Medical Center Cape Girardeau Missouri USA

7. Department of Medicine, Division of Hematology and Oncology Vanderbilt University Medical Center Nashville Tennessee USA

8. Department of Biostatistics, College of Public Health and Health Professions & College of Medicine University of Florida Gainesville Florida USA

9. Cardio‐Oncology Working Group UF Health Cancer Center Gainesville Florida USA

Abstract

AbstractAs a treatment for relapsed or refractory multiple myeloma (MM), carfilzomib has been associated with a significant risk of cardiovascular adverse events (CVAE). The goals of our study were to evaluate the metabolomic profile of MM patients to identify those at high risk prior to carfilzomib treatment and to explore the mechanisms of carfilzomib‐CVAE to inform potential strategies to protect patients from this cardiotoxicity. Global metabolomic profiling was performed on the baseline and post‐baseline plasma samples of 60 MM patients treated with carfilzomib‐based therapy, including 31 who experienced CVAE, in a prospective cohort study. Baseline metabolites and post‐baseline/baseline metabolite ratios that differ between the CVAE and no‐CVAE patients were identified using unadjusted and adjusted methods. A baseline metabolomic risk score was created to stratify patients. We observed a lower abundance of tauroursodeoxycholic acid (T‐UDCA) in CVAE patients at baseline (odds ratio [OR] = 0.47, 95% confidence interval [CI] = 0.21–0.94, p = 0.044) compared with the no‐CVAE patients. A metabolite risk score was able to stratify patients into three risk groups. The area under the receiver‐operating curve of the model with clinical predictors and metabolite risk score was 0.93. Glycochenodeoxycholic acid (OR = 0.56, 95% CI = 0.31–0.87, p = 0.023) was significantly lower in post‐baseline/baseline ratios of CVAE patients compared with no‐CVAE patients. Following metabolomic analysis, we created a baseline metabolite risk score that can stratify MM patients into different risk groups. The result also provided intriguing clues about the mechanism of carfilzomib‐CVAE and potential cardioprotective strategies.

Publisher

Wiley

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3