Monoclonal gammopathy of undetermined significance

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder present in 2.4% of the general population over the age of 50 years. MGUS is defined as the presence of a monoclonal protein <3.0 g/dL, <10% clonal plasma cells in the bone marrow, and absence of plasma cell-related end-organ damage. Multiple myeloma is consistently preceded by MGUS but the majority of patients with MGUS will never develop malignant disease. There are three major types of MGUS: non-IgM MGUS, IgM MGUS, and light-chain MGUS which typically progress to multiple myeloma, Waldenström’s macroglobulinemia, and light-chain multiple myeloma, respectively. The etiology of MGUS is largely unknown but male gender, ethnicity, previous autoimmune disease, and exposure to certain pesticides have been associated with increased risk of developing MGUS. Patients with MGUS are in the majority of cases asymptomatic but increased risks of comorbidities such as thrombosis, infection, and skeletal fractures have been observed. The risk of progression from MGUS to multiple myeloma and other lymphoproliferative disorders is approximately 0.5-1% per year and persists throughout follow-up why these patients need to be continuously monitored. The risk of progression can be predicted using different risk scores largely based on biomarkers: M-protein characteristics, uninvolved immunoglobulins and free light chains, as well as aberrant plasma cells in the bone marrow. Nevertheless, there is a need for development of molecular markers to better predict individual risk of progression. This chapter discusses disease definition, risk of progression, and clinical implications in patients with MGUS.