MGUS and Smoldering Multiple Myeloma: Diagnosis and Epidemiology

Monoclonal gammopathy of undetermined significance (MHUS) is characterized by the presence of a serum M-protein less than 3 g/dL, less than 10 % clonal plasma cells in the bone marrow, and the absence of myeloma-defining event. Smoldering multiple myeloma (SMM) is an asymptomatic disorder characterized by the presence of ≥3 g/dL serum M-protein and/or 10-60 % bone marrow plasma cell infiltration with no myeloma-defining event. The risk of progression to multiple myeloma (MM) requiring therapy varies greatly for individual patients, but it is uniform and 1 % per year for MGUS, while higher (10 % per year) and not uniform for SMM patients. The definition of MM was recently revisited patients previously labeled as SMM with a very high risk of progression (80-90 % at 2 years) were included in the updated definition of MM requiring therapy. The standard of care is observation for MGUS patients and although this also applies for SMM, a recent randomized trial targeting high-risk SMM showed that early intervention was associated with better progression-free and overall survival. Biomarkers have become an integrated part of diagnostic criteria for MM requiring therapy, as well as clinical risk stratification of patients with SMM. This paper reviews and discusses clinical implications for MGUS and SMM patients.