MGUS is a benign gammopathy defined by the presence of a monoclonal (M) protein less than 3 gm/dL, a bone marrow plasma cell concentration less than 10%, and an absence of symptoms of a monoclonal gammopathy (multiple myeloma, Waldenstrom's macroglobulinemia, amyloidosis, chronic lymphocytic leukemia, or B-cell lymphoma). The presence of hypercalcemia, renal insufficiency, anemia, and bone pain are indicative of an underlying malignant gammopathy. MGUS increases in frequency with advancing age. It is more common in men than women, and in persons of African heritage. MGUS may occur at a younger age and with a higher incidence in immunocompromised patients. While only a portion of cases of MGUS progress to multiple myeloma, the majority of cases of multiple myeloma are preceded by MGUS or smouldering myeloma.

MGUS should be suspected when a patient of appropriate age presents with an asymptomatic elevation of the total protein concentration. This should prompt further evaluation with an SPEP, UPEP, serum free light chain assay, and a 24-hour urinary protein level. If the SPEP reveals an M protein, then immunofixation will reveal the immunoglobulin type. Bone marrow biopsy with CD 138 staining of the marrow core is used to determine the percentage of plasma cells. Screening for end organ damage entails a CBC (to evaluate for anemia), BUN/Cr (to evaluate for renal impairment), serum calcium determination (evaluate for hypercalcemia) and a skeletal survey to evaluate for lytic bone lesions. An M protein concentration of 1.5 g/dL or higher, non-IgG MGUS, and an abnormal free light chain ratio (<0.26 or >1.65) are risk factors for progression. If flow cytometry is used to assay the bone marrow aspirate, then 95% or greater neoplastic plasma cell concentration or the presence of DNA aneuploidy are risk factors for progression.

Observation on a regular basis for symptoms of a monoclonal gammopathy or an increase in the M protein concentration is all that is required for these patients. Patients at low risk for progression by the above criteria should undergo evaluation with SPEP, CBC, calcium and creatinine at six months after the initial evaluation/diagnosis and then every two to three years. Since MGUS can progress at any time to a malignant condition, there is never an appropriate amount of time at which surveillance may be discontinued. There is an increased risk of osteoporosis with MGUS and patients should be screened and treated appropriately. Also, there is a higher incidence of both arterial and venous thrombotic disease with MGUS.

Smouldering myeloma, like MGUS, is an asymptomatic gammopathy; however, there is either an M protein level greater than 3 gm/dL or a bone marrow plasma cell concentration greater than 10%, or both. Smouldering myeloma progresses to multiple myeloma at a greater rate than MGUS. Currently no therapy is recommended. The initial evaluation is the same as for MGUS along with a baseline bone marrow biopsy followed by repeat surveillance labs at four to six month intervals for the first year and then every six to 12 months thereafter.