Lead Investigator: Fredrik Schjesvold, Oslo University Hospital
Title of Proposal Research: Personalized prediction of progression-free survival in multiple myeloma patients treated with isatuximab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone only, using combined machine learning and mechanistic modeling.
Vivli Data Request: 8609
Funding Source: None
Potential Conflicts of Interest: Received honorarium from Sanofi, Janssen, BMS, Oncopeptides, Abbvie, GSK, Pfizer. These conflicts of interest will be declared in any subsequent publications.
Summary of the Proposed Research:
Multiple myeloma (MM) is a cancer that originates in plasma cells, a type of white blood cells, in the bone marrow. MM is treatable, but remains largely incurable, and according to Cancer.net, an estimated 176.404 new cases were diagnosed worldwide in 2020. The disease is typically marked by recurrent episodes of remission and relapse that are difficult to predict. The combination of new drugs like isatuximab with pre-existing drugs has improved response rates, but the possible benefits of personalizing the drug combination has not been sufficiently explored. A particular goal of this study is to investigate the potential of personalizing the choice between pomalidomide or carfilzomib, two widely used treatments, when combined with isatuxumab and dexamethasone. Isatuximab works by binding to a protein called CD38 on the surface of MM cells, which promotes cell death in several ways, including attraction of immune cells that kill the MM cell. Pomalidomide, an immunomodulatory drug, increases the proliferation of T-cells that kill MM cells, while Carfilzomib blocks an intra-cellular protein complex called the proteasome in MM cells, thereby disrupting the regulation of proteins in the cell and promoting cell death. Dexamethasone is a steroid whose exact mechanism of action is unknown but is thought to promote MM cell death by interfering with the DNA transcription. This project utilizes patient characteristics, treatment history and longitudinal measurements obtained from patients under MM treatment with dexamethasone in combination with either pomalidomide or carfilzomib, with or without the addition of isatuximab, to develop computational tools able to predict treatment relapses in individual patients. To create predictions from this data, machine learning and mathematical modeling techniques will be utilized together. The resulting algorithm will be used to predict clinical outcomes of future patients treated with the therapies used in the clinical trials and may assist in the design of future personalized treatment strategies.
Requested Studies:
A Phase 3 Randomized, Open-label, Multicenter Study Comparing Isatuximab (SAR650984) in Combination With Pomalidomide and Low-Dose Dexamethasone Versus Pomalidomide and Low-Dose Dexamethasone in Patients With Refractory or Relapsed and Refractory Multiple Myeloma
Data Contributor: Sanofi
Study ID: NCT02990338
Sponsor ID: EFC14335
Randomized, Open Label, Multicenter Study Assessing The Clinical Benefit Of Isatuximab Combined With Carfilzomib (Kyprolis®) And Dexamethasone Versus Carfilzomib With Dexamethasone In Patients With Relapse And/Or Refractory Multiple Myeloma Previously Treated With 1 to 3 Prior Lines
Data Contributor: Sanofi
Study ID: NCT03275285
Sponsor ID: EFC15246