Identifying Optimal Panobinostat Treatment Regimens Utilizing Reverse-Engineered Concentration-Time Curves

Overview

Sudalagunta Moffitt Cancer Center The Ex Vivo Mathematical Malignancy Advisor Model (EMMA) is a support tool for treating Multiple Myeloma. A biopsy is taken, and patient plasma cells are cultured in plates to which chemotherapies are applied. These plates are imaged, and an algorithm produces a cell viability curve for each plate. EMMA is fit to these curves, and parameterizes patient-specific models of chemosensitivity to each tested chemotherapy. For EMMA to predict patient response to a specific chemotherapy, the model must incorporate that chemotherapy’s concentration -time curves (CTCs). These describe the average temporal variation in concentration doses of a specified chemotherapy will undergo in humans. Because CTCs aren’t readily accessible to the public, a novel mathematical model was formulated to reconstruct the CTCs of orally-administered Panobinostat. Model parameters were fit by minimizing the residual between the 20mg model curve’s cmax, t max, and AUC inf metrics, from those publicly provided about Panobinostat’s 20mg CTC. For the reconstructed CTCs of different doses, the model was solved using a different dosage value, and cmax, t max, and AUC inf were checked to ensure they fell within the reported range. Model CTCs were concatenated to create alternative treatment schedules. Using each logged patient’s chemosensitivity model, alternative treatment schedules were substituted and EMMA was run to produce best response: the predicted largest percent reduction in tumor volume that patient will experience. For 51.4% of patients, treatment scheduling produced best response metrics varied such that they were not all >50% or <5%. This indicates for half of patients, Panobinostat scheduling can be optimized.

Competition history

• JSHS 2020 Category not listed

Resources

• National JSHS abstract book ↗

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