Monoclonal gammopathy of undetermined significance: predictors of malignant transformation and recognition of an evolving type characterized by a progressive increase in M protein size

Mayo Clin Proc. 2007 Apr;82(4):428-34. doi: 10.4065/82.4.428.


Objective: To investigate the predictors of monoclonal gammopathy of undetermined significance (MGUS) by considering not only the initial features but also the pattern of evolution of the M protein during the first years after diagnosis.

Patients and methods: This study consisted of 359 patients diagnosed as having MGUS at a single institution. Patients who showed a definite and progressive increase in their M protein size according to serum electrophoresis during the first 3 years of follow-up were considered to have evolving MGUS, whereas all others were considered to have nonevolving MGUS.

Results: Of the 359 patients, 330 had nonevolving MGUS, whereas 29 fulfilled the criteria for evolving MGUS. Overall, 32 patients developed malignant transformation. The progression rates at 10 and 20 years of follow-up for the evolving and the nonevolving types were 55% vs 10% and 80% vs 13%, respectively. Multivariate analysis revealed that the features significantly associated with a higher risk of progression were evolving MGUS (relative risk [RR], 12.14; P<.001), IgA MGUS (RR, 2.93; P=.006), and M protein concentration (RR, 2.18; P=.04).

Conclusion: The evolutionary pattern of serum M protein (progressive increasing vs stable) during the first years of follow-up is the most important risk factor for disease progression in patients with MGUS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Transformation, Neoplastic / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin A / analysis
  • Immunoglobulin G / analysis
  • Immunoglobulins / analysis*
  • Male
  • Middle Aged
  • Monoclonal Gammopathy of Undetermined Significance / blood
  • Monoclonal Gammopathy of Undetermined Significance / mortality
  • Monoclonal Gammopathy of Undetermined Significance / pathology*
  • Risk Factors


  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulins