Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma

ABSTRACT: Multiple myeloma (MM) is a plasma cell malignancy defined by complex genetics and extensive patient heterogeneity. Despite a growing arsenal of approved therapies, MM remains incurable and in need of guidelines to identify effective personalized treatments. Here, we survey the ex vivo drug and immunotherapy sensitivities across 101 bone marrow (BM) samples from 70 MM patients using multiplexed immunofluorescence, automated microscopy and deep learning-based single-cell phenotyping. Combined with sample-matched genetics, proteotyping, and cytokine profiling, we map the molecular regulatory network of drug sensitivity, implicating the DNA-repair pathway and EYA3 expression in proteasome inhibitor sensitivity, and MHC class II expression in the response to Elotuzumab. Globally, ex vivo drug sensitivity associated with BM microenvironmental signatures reflecting treatment stage, clonality, and inflammation. Furthermore, ex vivo drug sensitivity significantly stratified clinical treatment responses, including to immunotherapy. Taken together, our study provides molecular and actionable insights into diverse treatment strategies for multiple myeloma patients.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Bernd Wollscheid  

PROVIDER: MSV000088992 | MassIVE | Sun Mar 06 15:08:00 GMT 2022

REPOSITORIES: MassIVE