Ex Vivo Drug Screening Assay Could Help Identify Best Myeloma Therapies for Each Patient

Researchers have developed a new tool designed to potentially help clinicians select the best treatments for patients with multiple myeloma.

Rafael Renatino-Canevarolo, PhD, of Moffitt Cancer Center in Tampa, Florida, and colleagues presented information at the 65th ASH Annual Meeting and Exposition on the Ex Vivo Mathematical Myeloma Advisor (EMMA), a platform designed to run “in silico clinical trials” on bone marrow samples taken from patients with multiple myeloma.

The platform works by taking fresh, bone marrow–derived multiple myeloma blasts combined with stromal cells in a collagen-based, matrix-containing patient plasma for use in an ex vivo drug screening assay. The cells are put in well plates and exposed to serial dilutions of up to 127 single agents and combinations, then imaged in a bright field every 30 minutes for six days.

Based on information gained from these images, resistant subclones can be identified. The data also are combined with augmented synergy models that are parameterized with pharmacokinetic and pharmacodynamic data for each drug or drug combination tested.

“The integration of clinical, molecular, and phenotypic data with image analysis and machine learning tools presents a unique opportunity for finding molecular signatures of drug response,” Dr. Renatino-Canevarolo and colleagues wrote in their abstract. “For instance, our pipeline can be utilized to identify clinical factors (such as ethnicity, age, etc) and molecular features (mutations, cytogenetic abnormalities, enriched transcription factors, differentially expressed biological pathways, etc.) associated with drug resistance/sensitivity.”

To date, EMMA has shown efficacy in quantifying the activity of monoclonal antibodies. Moving forward, the researchers want to focus on incorporating individual immune cell components to assess the ex vivo activity of cellular immunotherapies.

The researchers highlighted potential uses of EMMA, such as enabling pharmaceutical companies to test new compounds on patient-derived models, assisting clinicians in selecting the best therapies for their patients, and preventing cancer patients from receiving non-suitable therapies.

Reference

Renatino-Canevarolo R, Silva M, Meads MB, et al. Ex Vivo Mathematical Myeloma Advisor (EMMA) – a clinical, molecular, and phenotypic platform to tailor personalized therapeutic strategies for multiple myeloma. Abstract #2280. Presented at the 65th ASH Annual Meeting and Exposition; December 9–12, 2023; San Diego, California.