title: A Tumor Growth Inhibition Model Based on M-Protein Levels in Subjects With Relapsed/Refractory Multiple Myeloma Following Single-Agent Carfilzomib Use.
abstract: Change in tumor size estimated using longitudinal tumor growth inhibition (TGI) modeling is an early predictive biomarker of clinical outcomes for multiple cancer types. We present the application of TGI modeling for subjects with multiple myeloma (MM). Longitudinal time course changes in M-protein data from relapsed and/or refractory MM subjects who received single-agent carfilzomib in phase II studies (n = 456) were fit to a TGI model. The tumor growth rate estimate was similar to that of other anti-myeloma agents, indicating that the model is robust and treatment-independent. An overall survival model was subsequently developed, which showed that early change in tumor size (ECTS) at week 4, Eastern Cooperative Oncology Group performance status (ECOG PS), hemoglobin, sex, percent bone marrow cell involvement, and number of prior regimens were significant independent predictors for overall survival (P < 0.001). ECTS based on M-protein modeling could be an early biomarker for survival in MM following exposure to single-agent carfilzomib.
authors.affiliation: Pharsight, a Certara company St. Louis Missouri USA.
authors.forename: F
authors.initials: F
authors.lastname: Jonsson
authors.affiliation: Onyx Pharmaceuticals, Inc., an Amgen subsidiary South San Francisco California USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Ou
authors.affiliation: Pharsight, a Certara company St. Louis Missouri USA.
authors.forename: L
authors.initials: L
authors.lastname: Claret
authors.affiliation: John Theurer Cancer Center Hackensack New Jersey USA.
authors.forename: D
authors.initials: D
authors.lastname: Siegel
authors.affiliation: Mount Sinai Medical Center New York New York USA.
authors.forename: S
authors.initials: S
authors.lastname: Jagannath
authors.affiliation: Washington University School of Medicine St. Louis Missouri USA.
authors.forename: R
authors.initials: R
authors.lastname: Vij
authors.affiliation: Greenebaum Cancer Center University of Maryland Baltimore Maryland USA.
authors.forename: A
authors.initials: A
authors.lastname: Badros
authors.affiliation: Onyx Pharmaceuticals, Inc., an Amgen subsidiary South San Francisco California USA.
authors.forename: S
authors.initials: S
authors.lastname: Aggarwal
authors.affiliation: Pharsight, a Certara company St. Louis Missouri USA.
authors.forename: R
authors.initials: R
authors.lastname: Bruno