Monoclonal Gammopathy of Undetermined Significance: Current Concepts and Future Prospects

Purpose of the Review: Monoclonal gammopathy of undetermined significance (MGUS) is a highly prevalent precursor condition in the general population, with an approximate 1% annual risk of progression to multiple myeloma (MM) or a related disorder. Our understanding of MGUS and its association with myriad clinical disorders, its progression to MM, and the genomic alterations in the setting of a conducive or permissive microenvironment has deepened considerably. Recent Findings: Data from gene expression profiling studies have underscored the heterogeneity in the risk of progression of MGUS to MM. Ongoing efforts are being directed toward precise identification of high-risk factors for progression and addressing the role of screening for MGUS in populations at higher risk of MGUS in order to diagnose this precursor condition early, and target modifiable risk factors. Ongoing clinical trials are assessing the role of therapeutic interventions to prevent MGUS from progressing. Summary: MGUS is a heterogeneous precursor condition with a risk for progression to symptomatic disease. Future directions are focusing on identifying high-risk populations of MGUS and smoldering multiple myeloma that may benefit with screening and/or early intervention.