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

Diagnostic Criteria

MGUS is diagnosed when all three of the following criteria are met: serum monoclonal protein < 3 g/dL, clonal bone marrow plasma cells < 10%, and absence of end-organ damage (CRAB criteria) attributable to a plasma cell proliferative disorder 1, 2, 3
The diagnostic criteria include serum monoclonal protein < 3 g/dL, clonal bone marrow plasma cells < 10%, and absence of CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone lesions) 1, 2, 3
Abnormal free light chain (FLC) ratio (<0.26 or >1.65) and increased level of involved light chain are also considered in the diagnosis of MGUS 3

Risk factors for progression to multiple myeloma or related disorders include serum M protein level ≥ 1.5 g/dL, non-IgG isotype (IgA or IgM), and abnormal free light chain ratio 3
The risk groups for progression are: low risk (no risk factors): 2% lifetime risk of progression, low-intermediate risk (1 factor): 10% risk at 20 years, high-intermediate risk (2 factors): 18% risk at 20 years, and high risk (all 3 factors): 27% risk at 20 years 3

MGUS must be differentiated from multiple myeloma, which is characterized by serum M protein ≥ 3 g/dL and/or clonal bone marrow plasma cells ≥ 10%, and presence of CRAB criteria 3
The CRAB criteria include hypercalcemia (serum calcium > 11.5 mg/dL), renal insufficiency (serum creatinine > 2 mg/dL or creatinine clearance < 40 mL/min), anemia (hemoglobin < 10 g/dL or > 2 g/dL below lower limit of normal), and bone lesions (lytic lesions, severe osteopenia, or pathologic fractures) 3

Baseline bone marrow examination and skeletal radiography are not routinely indicated if clinical evaluation and blood tests suggest MGUS, but follow-up with serum protein electrophoresis at 6 months is recommended 3
If stable, follow-up every 2-3 years or when symptoms suggestive of plasma cell malignancy arise, and baseline bone marrow aspirate and biopsy are recommended for further evaluation 3
Cytogenetics and FISH should be performed, and follow-up with serum protein electrophoresis and complete blood count at 6 months, then annually for life 3