title: AnEx VivoPlatform for the Prediction of Clinical Response in Multiple Myeloma.
abstract: Multiple myeloma remains treatable but incurable. Despite a growing armamentarium of effective agents, choice of therapy, especially in relapse, still relies almost exclusively on clinical acumen. We have developed a system,Ex vivoMathematical Myeloma Advisor (EMMA), consisting of patient-specific mathematical models parameterized by anex vivoassay that reverse engineers the intensity and heterogeneity of chemosensitivity of primary cells from multiple myeloma patients, allowing us to predict clinical response to up to 31 drugs within 5 days after bone marrow biopsy. From a cohort of 52 multiple myeloma patients, EMMA correctly classified 96% as responders/nonresponders and correctly classified 79% according to International Myeloma Working Group stratification of level of response. We also observed a significant correlation between predicted and actual tumor burden measurements (Pearsonr= 0.5658,P< 0.0001). Preliminary estimates indicate that, among the patients enrolled in this study, 60% were treated with at least one ineffective agent from their therapy combination regimen, whereas 30% would have responded better if treated with another available drug or combination. Twoin silicoclinical trials with experimental agents ricolinostat and venetoclax, in a cohort of 19 multiple myeloma patient samples, yielded consistent results with recent phase I/II trials, suggesting that EMMA is a feasible platform for estimating clinical efficacy of drugs and inclusion criteria screening. This unique platform, specifically designed to predict therapeutic response in multiple myeloma patients within a clinically actionable time frame, has shown high predictive accuracy in patients treated with combinations of different classes of drugs. The accuracy, reproducibility, short turnaround time, and high-throughput potential of this platform demonstrate EMMA's promise as a decision support system for therapeutic management of multiple myeloma.Cancer Res; 77(12); 3336-51. ©2017 AACR.
authors.affiliation: Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Ariosto
authors.initials: A
authors.lastname: Silva
authors.affiliation: Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Silva
authors.affiliation: Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Praneeth
authors.initials: P
authors.lastname: Sudalagunta
authors.affiliation: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Allison
authors.initials: A
authors.lastname: Distler
authors.affiliation: Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Timothy
authors.initials: T
authors.lastname: Jacobson
authors.affiliation: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Aunshka
authors.initials: A
authors.lastname: Collins
authors.affiliation: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Tuan
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Department of Hematologic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Jinming
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Statistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Dung-Tsa
authors.initials: DT
authors.lastname: Chen
authors.affiliation: Department of Statistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Translational Medicine Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Christopher
authors.initials: C
authors.lastname: Cubitt
authors.affiliation: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Rachid
authors.initials: R
authors.lastname: Baz
authors.affiliation: Department of Bone Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Lia
authors.initials: L
authors.lastname: Perez
authors.affiliation: nPharmakon, LLC, Piscataway, New Jersey.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Rebatchouk
authors.affiliation: M2Gen, Tampa, Florida.
authors.forename: William
authors.initials: W
authors.lastname: Dalton
authors.affiliation: Rutgers, New Brunswick, NJ.
authors.forename: James
authors.initials: J
authors.lastname: Greene
authors.affiliation: Department of Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Robert
authors.initials: R
authors.lastname: Gatenby
authors.affiliation: Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Robert
authors.initials: R
authors.lastname: Gillies
authors.affiliation: Rutgers, New Brunswick, NJ.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sontag
authors.affiliation: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.|Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Meads
authors.affiliation: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. ken.shain@moffitt.org.|Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Shain
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003661:Decision Support Techniques; D057166:High-Throughput Screening Assays; D006801:Humans; D008962:Models, Theoretical; D009101:Multiple Myeloma / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents