Ex Vivo Modeling of Multiple Myeloma: A Novel Drug Sensitivity Screening Platform

Multiple Myeloma (MM) is the second most common hematologic malignancy, after non-Hodgkin’s lymphoma. This debilitating disease globally affects 1 to 5 people in every 100,000 people each year. After initial diagnosis, the 5-year survival rate is 44% because there is no curative therapy, and most patients will eventually experience relapse, and some become refractory. Approximately 75,000 patients around the world are living with relapsed or refractory MM. There are an estimated 34,470 new cases of MM by 2022 and an estimated 12,640 new deaths in 2022.

MM is a heterogeneous malignancy characterized by abnormal clonal plasma cell infiltration in the bone marrow. The clinical manifestations of the disease are driven by monoclonal protein, the malignant cells or cytokines secreted by the malignant cells, and include Calcemia, Renal insufficiency, Anemia, and Bone disease with lytic lesions.

MM development is a multistep process, which starts with precursor disease states, such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Primary genetic events in the development of MGUS, SMM, and MM include chromosomal translocations involving the immunoglobulin heavy-chain genes (IGH) and aneuploidy. The number of secondary genetic alterations increases from MGUS to SMM and then to multiple myeloma. 

Large inter-patient and intra-patient genetic heterogeneity limit the identification of universal drivers of MM. However, several oncogenic dependencies such as primary events related to driver gene mutations and primary translocations can be targeted for better treatment strategies for R/R multiple myeloma.

Therefore a robust drug sensitivity screening platform using well-characterized primary Multiple Myeloma patient samples is needed.