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MGUS Management

Monoclonal Gammopathy of Unknown Significance (MGUS) is a term coined by Dr. Robert A Kyle (Amer J Med 1978;64:814-26). Prior to then, this entity was called benign monoclonal gammopathy. Since Dr. Kyle found a 1% per year risk of progression to myeloma, he felt it the word “benign” did not accurately capture the clinical implications.

MGUS is detected by serum protein electrophoresis as a monoclonal, or M, spike.  Immunofixation electrophoresis (IFE) is subsequently performed to determine if the monoclonal protein is IgG or IgM or IgA, kappa or lambda. MGUS is defined by an M protein less than 3 gm per dL, and no myeloma defining events (MDE). 

MGUS was first estimated to be present in 3% of the population above the age of 50. The addition of free light chain analysis has increased the prevalence to 5% in the people over the age of 50. Prevalence of is 2 to 3 times higher in first degree relatives of people with MGUS or myeloma. It is important to realize that myeloma incidence is only 4 cases per 100,000 people per year, so a 3 fold higher is 12 cases per 100,000 people per year, which is still a low risk. Prevalence of MGUS is also 2 to 3-fold higher in Black people. The higher prevalence of MGUS in Black people is the main reason for the higher prevalence of myeloma in this population. MGUS also occurs at an earlier age in Black people.

MGUS is associated with an approximately 1% risk per year of progression to myeloma or a related disorder. The progression risk persists indefinitely but people are susceptible to many other diseases the real risk of progression of MGUS to myeloma over a lifetime is only 10%. That is, 90% of patients with MGUS will never progress to myeloma, Waldenstroms, plasmacytoma, or amyloidosis.

If MGUS is suspected, not everyone needs a bone marrow aspirate and biopsy or bone survey. The yield of these tests in low-risk patients is close to zero.

All patients with a new diagnosis of MGUS should have a CBC, creatinine, calcium, serum protein electrophoresis and serum free light chain assay rechecked in 6 months. If these values remain stable, additional followup can be scheduled yearly or if symptoms occur.


How I manage monoclonal gammopathy of undetermined significance, Ronald Go and Vincent Rajkumar, Blood (2018) 131 (2): 163–173.

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