Venetoclax ex vivo functional profiling predicts improved progression-free survival

• Type of Material: Article
• Authors: Vikas Gupta, Emory University; Shannon Matulis, Emory University; Benjamin Barwick, Emory University; R. Devin Bog, Emory University; Conrad W. Shebelut, Emory University; Malathy Shanmugam, Emory University; Paola Neri, University of Calgary; Nizar J. Bahlis, University of Calgary; Madhav Dhodapkar, Emory University; Leonard T. Heffner, Emory University; Craig Hofmeister, Emory University; Nisha Joseph, Emory University; Sagar Lonial, Emory University; Jonathan Kaufman, Emory University; David Jaye, Emory University; Ajay Nooka, Emory University; Lawrence Boise, Emory University
• Language: English
• Date: 2022-08-04
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41408-022-00710-9
• Title of Journal or Parent Work: Blood Cancer Journal
• Volume: 12
• Issue: 8
• Grant/Funding Information: Supported in part by grants R01 CA192844 and P30CA138292, the MMRF Answer Fund, Winship Cancer Institute #IRG-14-188-01 from the American Cancer Society, and the Riney Family Foundation. Research reported in this publication was supported in part by the Winship Cancer Institute of Emory University Cancer Tissue and Pathology shared resource as well as the Winship Data and Technology Applications Shared Resource and NIH/NCI under award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
• Research Categories: Biology, Cell; Health Sciences, Oncology

Abstract

In multiple myeloma, the t(11;14) translocation enriches for patients likely to respond to the Bcl2 inhibitor venetoclax. In this group of patients, 40% respond to single-agent venetoclax while up to 60% respond to the combination of venetoclax and dexamethasone [1, 2]. We have previously demonstrated that ex vivo functional profiling of venetoclax sensitivity can more accurately identify these venetoclax-responsive patients [3]. Here we report updated data on a larger cohort of patients who underwent ex vivo testing and were subsequently treated with venetoclax. We demonstrate that this 24-hour functional assay can rapidly predict patient responses to venetoclax that translate into improved progression-free survival (PFS).