Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma
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Date
2023-05
Publication Type
Journal Article
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yes
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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 samples from 70 patients with MM 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 major histocompatibility complex class II expression in the response to elotuzumab. Globally, ex vivo drug sensitivity associated with bone marrow 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 patients with MM.
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published
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Journal / series
Volume
4 (5)
Pages / Article No.
734 - 753
Publisher
Nature
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Date created
Subject
Organisational unit
09595 - Snijder, Berend (ehemalig) / Snijder, Berend (former)
02072 - Proteomics Plattform D-HEST
02540 - Institut für Translationale Medizin / Institute of Translational Medicine
Notes
Funding
803063 - Studying Cancer Individuality by Personal and Predictive Drug Screening and Differential OMICs (EC)