Determining optimal combination regimens for patients with multiple myeloma

Eur J Pharm Sci. 2023 Aug 1:187:106492. doi: 10.1016/j.ejps.2023.106492. Epub 2023 Jun 9.


While many novel therapies have been approved in recent years for treating patients with multiple myeloma, there is still no established curative regimen, especially for patients with high-risk disease. In this work, we use a mathematical modeling approach to determine combination therapy regimens that maximize healthy lifespan for patients with multiple myeloma. We start with a mathematical model for the underlying disease and immune dynamics, which was presented and analyzed previously. We add the effects of three therapies to the model: pomalidomide, dexamethasone, and elotuzumab. We consider multiple approaches to optimizing combinations of these therapies. We find that optimal control combined with approximation outperforms other methods, in that it can quickly produce a combination regimen that is clinically-feasible and near-optimal. Implications of this work can be used to optimize doses and advance the scheduling of drugs.

Keywords: Combination drug regimen; Constrained optimization; Mathematical model; Multiple myeloma; Optimal control.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Combined Modality Therapy
  • Dexamethasone / therapeutic use
  • Humans
  • Multiple Myeloma* / drug therapy


  • Dexamethasone