Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance

N Engl J Med. 2018 Jan 18;378(3):241-249. doi: 10.1056/NEJMoa1709974.


Background: Monoclonal gammopathy of undetermined significance (MGUS) occurs in approximately 3% of persons 50 years of age or older.

Methods: We studied 1384 patients who were residing in southeastern Minnesota and in whom MGUS was diagnosed at the Mayo Clinic in the period from 1960 through 1994; the median follow-up was 34.1 years (range, 0.0 to 43.6). The primary end point was progression to multiple myeloma or another plasma-cell or lymphoid disorder.

Results: During 14,130 person-years of follow-up, MGUS progressed in 147 patients (11%), a rate that was 6.5 times (95% confidence interval [CI], 5.5 to 7.7) as high as the rate in the control population. The risk of progression without accounting for death due to competing causes was 10% at 10 years, 18% at 20 years, 28% at 30 years, 36% at 35 years, and 36% at 40 years. Among patients with IgM MGUS, the presence of two adverse risk factors - namely, an abnormal serum free light-chain ratio (ratio of kappa to lambda free light chains) and a high serum monoclonal protein (M protein) level (≥1.5 g per deciliter) - was associated with a risk of progression at 20 years of 55%, as compared with 41% among patients who had one adverse risk factor and 19% among patients who had neither risk factor. Among patients with non-IgM MGUS, the risk of progression at 20 years was 30% among those who had the two risk factors, 20% among those who had one risk factor, and 7% among those who had neither risk factor. Patients with MGUS had shorter survival than was expected in the control population of Minnesota residents of matched age and sex (median, 8.1 vs. 12.4 years; P<0.001).

Conclusions: Significant differences were noted in the risk of progression between patients with IgM MGUS and those with non-IgM MGUS. Overall survival was shorter among patients with MGUS than was expected in a matched control population. (Funded by the National Cancer Institute.).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Bone Marrow Examination
  • Disease Progression*
  • Female
  • Follow-Up Studies
  • Glycoproteins / blood
  • Humans
  • Immunoglobulin Light Chains / blood
  • Immunoglobulin M / blood
  • Male
  • Middle Aged
  • Monoclonal Gammopathy of Undetermined Significance / complications*
  • Monoclonal Gammopathy of Undetermined Significance / mortality
  • Monoclonal Gammopathy of Undetermined Significance / pathology
  • Multiple Myeloma / etiology
  • Prognosis
  • Proportional Hazards Models
  • Risk Factors


  • Glycoproteins
  • Immunoglobulin Light Chains
  • Immunoglobulin M
  • protein M (glycoprotein)