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Multiple myeloma gammopathies

Changing paradigms in diagnosis and treatment of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM)

Leukemia volume 34, pages 3111–3125 (2020)Cite this article

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Abstract

Multiple myeloma (MM) is a highly heterogenous disease that exists along a continuous disease spectrum starting with premalignant conditions monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) that inevitably precede MM. Over the past two decades, significant progress has been made in the genetic characterization and risk stratification of precursor plasma cell disorders. Indeed, the clinical introduction of highly effective and well-tolerated drugs begs the question: would earlier therapeutic intervention with novel therapies in MGUS and SMM patients alter natural history, providing a potential curative option? In this review, we discuss the epidemiology of MGUS and SMM and current models for risk stratification that predict MGUS and SMM progression to MM. We further discuss genetic heterogeneity and clonal evolution in MM and the interplay between tumor cells and the bone marrow (BM) microenvironment. Finally, we provide an overview of the current recommendations for the management of MGUS and SMM and discuss the open controversies in the field in light of promising results from early intervention clinical trials.

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Fig. 1: Clinical model of disease progression in MM: the IMWG diagnostic criteria.
Fig. 2: Clonal model of disease progression in MM.

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  1. These authors contributed equally: Ashish Patel, Chia Yin Goh

Authors and Affiliations

  1. Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

    Matthew Ho

  2. Department of Internal Medicine, University of Toronto, Toronto, ON, Canada

    Ashish Patel

  3. University College Dublin School of Medicine and Medical Science, Dublin, Dublin, Ireland

    Chia Yin Goh

  4. Division of Hematology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

    Maria Moscvin & Giada Bianchi

  5. Department of Hematology, Sichuan University, Chengdu, Sichuan, 610041, China

    Li Zhang

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Ho, M., Patel, A., Goh, C.Y. et al. Changing paradigms in diagnosis and treatment of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Leukemia 34, 3111–3125 (2020). https://doi.org/10.1038/s41375-020-01051-x

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