A long-term study of prognosis in monoclonal gammopathy of undetermined significance

N Engl J Med. 2002 Feb 21;346(8):564-9. doi: 10.1056/NEJMoa01133202.


Background: A monoclonal gammopathy of undetermined significance (MGUS) occurs in up to 2 percent of persons 50 years of age or older. Reliable predictors of progression have not been identified, and information on prognosis is limited.

Methods: We identified 1384 patients residing in southeastern Minnesota in whom MGUS was diagnosed at the Mayo Clinic from 1960 through 1994. The primary end point was progression to multiple myeloma or another plasma-cell cancer.

Results: During 11,009 person-years of follow-up, MGUS progressed in 115 of the 1384 patients to multiple myeloma, IgM lymphoma, primary amyloidosis, macroglobulinemia, chronic lymphocytic leukemia, or plasmacytoma (relative risk of progression, 25.0, 2.4, 8.4, 46.0, 0.9, and 8.5, respectively). The overall relative risk of progression was 7.3 in these patients as compared with the white population of the Iowa Surveillance, Epidemiology, and End Results program. In 32 additional patients, the monoclonal protein concentration increased to more than 3 g per deciliter or the percentage of plasma cells in the bone marrow increased to more than 10 percent (smoldering multiple myeloma) but without progression to overt myeloma or related disorders. The cumulative probability of progression was 12 percent at 10 years, 25 percent at 20 years, and 30 percent at 25 years. The initial concentration of serum monoclonal protein was a significant predictor of progression at 20 years.

Conclusions: The risk of progression of MGUS to multiple myeloma or related disorders is about 1 percent per year.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Amyloidosis / etiology
  • Disease Progression
  • Follow-Up Studies
  • Humans
  • Leukemia, Lymphoid / etiology
  • Lymphoma / etiology
  • Middle Aged
  • Multiple Myeloma / etiology
  • Paraproteinemias* / complications
  • Paraproteinemias* / diagnosis
  • Paraproteinemias* / physiopathology
  • Probability
  • Prognosis
  • Risk Factors
  • Waldenstrom Macroglobulinemia / etiology