A monoclonal gammopathy precedes multiple myeloma in most patients

Blood. 2009 May 28;113(22):5418-22. doi: 10.1182/blood-2008-12-195008. Epub 2009 Feb 20.


Preexisting plasma cell disorders, monoclonal gammopathy of undetermined significance, or smoldering myeloma are present in at least one-third of multiple myeloma patients. However, the proportion of patients with a preexisting plasma cell disorder has never been determined by laboratory testing on prediagnostic sera. We cross-referenced our autologous stem cell transplantation database with the Department of Defense Serum Repository. Serum protein electrophoresis, immunofixation electrophoresis, and serum free light-chain analysis were performed on all sera collected 2 or more years before diagnosis to detect a monoclonal gammopathy (M-Ig). In 30 of 90 patients, 110 prediagnostic samples were available from 2.2 to 15.3 years before diagnosis. An M-Ig was detected initially in 27 of 30 patients (90%, 95% confidence interval, 74%-97%); by serum protein electrophoresis and/or immunofixation electrophoresis in 21 patients (77.8%), and only by serum free light-chain analysis in 6 patients (22.2%). Four patients had only one positive sample within 4 years before diagnosis, with all preceding sera negative. All 4 patients with light-chain/nonsecretory myeloma evolved from a light-chain M-Ig. A preexisting M-Ig is present in most multiple myeloma patients before diagnosis. Some patients progress rapidly through a premalignant phase. Light-chain detected M-Ig is a new entity that requires further study.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Early Detection of Cancer
  • Female
  • Humans
  • Immunoglobulins / analysis
  • Immunoglobulins / blood
  • Male
  • Middle Aged
  • Multiple Myeloma / blood
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / etiology*
  • Paraproteinemias / blood
  • Paraproteinemias / complications*
  • Paraproteinemias / diagnosis
  • Precancerous Conditions / blood
  • Precancerous Conditions / complications*
  • Precancerous Conditions / diagnosis*
  • Time Factors


  • Immunoglobulins