Management and Treatment of Monoclonal Gammopathy of Undetermined Significance (MGUS)

Diagnostic Evaluation

The International Myeloma Society recommends initial evaluation to include complete history and physical examination focusing on symptoms and signs suggestive of multiple myeloma, Waldenström macroglobulinemia, or AL amyloidosis 1, 3
Laboratory studies should include complete blood count, serum calcium, and creatinine 3, 4
Serum protein electrophoresis, immunofixation, and serum free light chain analysis are also recommended 1, 3
Quantitative tests for IgG, IgA, and IgM should be performed 1
Qualitative test for urine protein; if positive, perform urine electrophoresis and immunofixation 3

The Mayo Clinic risk stratification model should be used to assess the risk of progression to MM or related disorders 2, 6
Low risk is defined as IgG isotype, M-protein <15 g/L, and normal FLC ratio, with a 5% risk of progression at 20 years 7
Low-intermediate risk is defined as one risk factor present, with a 21% risk at 20 years 2
High-intermediate risk is defined as two risk factors present, with a 37% risk at 20 years 2
High risk is defined as three risk factors present, with a 58% risk at 20 years 2, 6, 7

Follow-up should be personalized based on risk stratification and life expectancy 2, 6
Low-risk MGUS patients should have initial follow-up at 6 months, and every 1-2 years thereafter if stable 2, 6, 7
Non-low-risk MGUS and Light-chain MGUS patients should have initial follow-up at 6 months, and annually thereafter 2, 6, 7
All MGUS types with life expectancy <5 years should not have routine follow-up, but additional investigations if symptoms suggestive of progression develop 2, 6

The International Myeloma Society recommends attention to disorders related to autoantibody activity of the M-protein, deposition of M-protein in tissues, and alterations in bone marrow microenvironment 8, 6, 4
Clone-directed therapy may be justified in rare cases of MGUS-related disorders 6, 4

There are currently no interventions to prevent or delay progression of MGUS, and any intervention approaches should only be performed in the setting of a clinical trial 2, 6

Screening of the general population for MGUS is not recommended outside of research studies, even among relatives of MGUS, MM, or WM patients 6, 7