Mathematical Optimization of a Thrombopoiesis Quantitative Systems Pharmacology (QSP) Model to Improve Chemotherapy Dosing
Alvaro Ruiz-Martinez, PhD, Senior Modeler, Rosa & Co. LLC
Dr. Alvaro Ruiz-Martinez has twelve years of computational and modeling experience related to mechanical, chemical, and biological systems. He has developed models focused on immuno-oncology, biopolymer assembly, and pharmacokinetics and pharmacodynamics. Dr. Ruiz-Martinez received his Ph.D. in Mechanical Engineering from the University of California, San Diego, and his postdoctoral degree from Johns Hopkins University.
Webinar Recording
Abstract:
Several QSP models have been developed over the years to better understand platelet dynamics and regulation of thrombopoiesis. Some models were able to reproduce observed oscillations in the platelet counts of normal humans, while others explored platelet dynamics in response to chemotherapy in cancer patients. Most of these models used complex mathematical representation, e.g., integro-differential equations. Here, we present an efficient fit-for-purpose thrombopoiesis QSP model, finding the minimal model structure still able to reproduce experimental data. We set three goals: simplification of parameters and equations, calibration to match platelet data, and evaluation of response to chemotherapy in a healthy virtual patient (VP) with normal platelet levels and in a thrombocytopenic VP representing acute myeloid leukemia (AML). The model was able to reproduce megakaryopoiesis timing and TPO dynamics and it was successfully tested for azacitidine (AZA) monotherapy and AZA + venetoclax combination therapy.