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

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, signific...

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Bibliographic Details
Published in:Leukemia 2020-12, Vol.34 (12), p.3111-3125
Main Authors: Ho, Matthew, Patel, Ashish, Goh, Chia Yin, Moscvin, Maria, Zhang, Li, Bianchi, Giada
Format: Article
Language:English
Subjects:
692/699/1541/1990/804
692/700/565/1436/2185
Benign monoclonal gammopathy
Bone marrow
Cancer
Cancer Research
Care and treatment
Clinical trials
Critical Care Medicine
Diagnosis
Disease Progression
Epidemiology
Evaluation
Health risk assessment
Hematology
Heterogeneity
Humans
Intensive
Internal Medicine
Medical diagnosis
Medicine
Medicine & Public Health
Monoclonal Gammopathy of Undetermined Significance - diagnosis
Monoclonal Gammopathy of Undetermined Significance - drug therapy
Monoclonal Gammopathy of Undetermined Significance - pathology
Multiple myeloma
Oncology
Oncology, Experimental
Review Article
Risk Factors
Smoldering
Smoldering Multiple Myeloma - diagnosis
Smoldering Multiple Myeloma - drug therapy
Smoldering Multiple Myeloma - pathology
Tumor cells
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Summary: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.
ISSN:0887-6924
1476-5551
DOI:10.1038/s41375-020-01051-x