In vitro testing of drug response in primary multiple myeloma cells using a microwell-based technology

Abstract

Multiple myeloma is an aggressive neoplasm of plasma cells. While numerous drugs have gained approval, the absence of established predictive markers for individual drug responses poses a challenge. In this study, we explored the microwell- and fluorescence-based Cellply CC-Array® technology for high-throughput analysis of in vitro drug responses as a potential predictive marker for patient treatment outcomes. Furthermore, we investigated its application for evaluating effector cell effectiveness. Mononuclear cells were isolated from the bone marrow of 22 patients, and in vitro drug response of primary myeloma cells was analyzed. In vitro responses towards melphalan, bortezomib, and dexamethasone in primary patient samples correlated with clinical response of the patients. The approach exhibited limitations in identifying sensitivity towards lenalidomide, daratumumab, and elotuzumab due to limited culturing time caused by poor myeloma viability in vitro. Through the analysis of cell proximity, the platform enabled the assessment of individual anti-tumor activity from NK and T cells. In summary, the CC-Array microwell technology allowed assessment of myeloma cell responses to selected drugs used in multiple myeloma therapy in vitro. To further validate these in vitro results against in vivo outcomes, screening a larger cohort is necessary.