Monoclonal Gammopathy Common in the Elderly

Abstract & Commentary

By Andrew S. Artz, MD, Section of Hematology/Oncology, University of Chicago. Dr. Artz reports no financial relationship to this field of study.

Synopsis: Among residents of Olmsted County, Minnesota, MGUS was found in 3.2 percent of persons 50 years of age or older and 5.3 percent of persons 70 years of age or older.

Source: Kyle RA, et al. Prevalence of Monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354:1362-1369.

Monoclonal gammopathy of undetermined significance (MGUS) is a common incidental finding but requires differentiation from multiple myeloma (MM). Distinguishing MGUS from MM once a serum or urine monoclonal protein has been detected requires a serum monoclonal protein concentration < 3 g/dL, fewer than 10% plasma cells in the bone marrow, and absence of lytic bone lesions, anemia, hypercalcemia or renal insufficiency related to a plasma cell disorder. MGUS remains a concern because of a heightened risk of progression to a plasma cell dyscrasia such as MM or primary amyloidosis. In the case of IgM MGUS, a lymphoproliferative disorder may subsequently develop. Prior reports have estimated the incidence of MGUS to occur in approximately 1-3% of adults and the risk of progression to a lymphoproliferative disorder after MGUS has been diagnosed at 1% annually.

This epidemiologic study evaluated the prevalence of MGUS among residents 50 years and older in Olmstead County, Minnesota. Serum samples were available for over 20,000 residents, encompassing most of the eligible residents. Immunofixation was performed on samples with an abnormality on serum electrophoresis.

MGUS was identified in 3.7% of men, 2.9% of women, and 3.2% among the entire cohort of 21,463 residents 50 years and older. Prevalence rose in concert with advancing age, from 1.6% for those 50 to 59 years rose to 6.6% for 80 years or older. Isotypes involved were IgG in 69%, IgM in 17%, IgA in 11% and biclonal in 3%. Kappa light chain occurred in 62% and lambda in 38%.

Commentary

The findings that the prevalence of MGUS increased with advanced age and was greater in men are not new, but confirm prior work. The IgG isotype accounted for the majority of cases.

Limitations from this observational study include lack of knowledge about what evaluation patients had for the monoclonal protein. Some may have had an incomplete evaluation and actually had MM or other plasma cell dyscrasia. Alternatively, MGUS may be under diagnosed as light chain only monoclonal proteins would be missed by this screening modality. The almost entirely Caucasian population prevents inferences into other ethnic or racial groups. This may be particularly problematic among African-Americans, a group where MGUS and MM occurs more commonly.

MGUS is a common laboratory abnormality, particularly in the elderly. A challenging task remains in determining how extensive an evaluation is necessary to exclude MM after finding a monoclonal protein. Clearly, in the presence of symptoms or other laboratory abnormalities (unexplained anemia, renal insufficiency, hypercalcemia, and significant urinary light chains) a complete evaluation is needed. Even with a negative evaluation, most would suggest following the monoclonal for evidence of progression. Risk factors previously published for progression to MM or other disorder include a serum M protein > 1.5 g/dL, a non-IgG monoclonal isotype, or an abnormal serum free light chain concentration ratio. In light of the numerous and effective therapies available for MM, recognition of MM is essential.