Data from An <i>Ex Vivo</i> Platform for the Prediction of Clinical Response in Multiple Myeloma

• DOI: 10.1158/0008-5472.c.6508731.v1
• Publication Date: 2023-03-31T22:28:52Z
• Authors: Ariosto Silva; Maria C. Silva; Praneeth Sudalagunta; Allison Distler; Timothy Jacobson; Aunshka Collins; Tuan Nguyen; Jinming Song; Dung-Tsa Chen; Lu Chen; Christopher Cubitt; Rachid Baz; Lia Perez; Dmitri Rebatchouk; William Dalton; James Greene; Robert Gatenby; Robert Gillies; Eduardo Sontag; Mark B. Meads; Kenneth H. Shain
• Keywords: Ex vivo; Regimen

&lt;div&gt;Abstract&lt;p&gt;Multiple myeloma remains treatable but incurable. Despite a growing armamentarium of effective agents, choice therapy, especially in relapse, still relies almost exclusively on clinical acumen. We have developed system, &lt;i&gt;Ex vivo&lt;/i&gt; Mathematical Myeloma Advisor (EMMA), consisting patient-specific mathematical models parameterized by an &lt;i&gt;ex assay that reverse engineers the intensity and heterogeneity chemosensitivity primary cells from multiple patients, allowing us to predict response up 31 drugs within 5 days after bone marrow biopsy. From cohort 52 EMMA correctly classified 96% as responders/nonresponders 79% according International Working Group stratification level response. also observed significant correlation between predicted actual tumor burden measurements (Pearson &lt;i&gt;r&lt;/i&gt; = 0.5658, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001). Preliminary estimates indicate that, among patients enrolled this study, 60% were treated with at least one ineffective agent their therapy combination regimen, whereas 30% would responded better if another available drug or combination. Two &lt;i&gt;in silico&lt;/i&gt; trials experimental agents ricolinostat venetoclax, 19 patient samples, yielded consistent results recent phase I/II trials, suggesting is feasible platform for estimating efficacy inclusion criteria screening. This unique platform, specifically designed therapeutic clinically actionable time frame, has shown high predictive accuracy combinations different classes drugs. The accuracy, reproducibility, short turnaround time, high-throughput potential demonstrate EMMA's promise decision support system management myeloma. &lt;i&gt;Cancer Res; 77(12); 3336–51. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;