Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: A prospective study

Ola Landgren, Robert A. Kyle, Ruth M. Pfeiffer, Jerry A. Katzmann, Neil E. Caporaso, Richard B. Hayes, Angela Dispenzieri, Shaji K Kumar, Raynell J. Clark, Dalsu Baris, Robert Hoover, S Vincent Rajkumar

Research output: Contribution to journalArticle

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Abstract

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma-cell proliferative disorder associated with a life-long risk of progression to multiple myeloma (MM). It is not known whether MM is always preceded by a premalignant asymptomatic MGUS stage. Among 77 469 healthy adults enrolled in the nationwide population-based prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we identified 71 subjects who developed MM during the course of the study in whom serially collected (up to 6) prediagnostic serum samples obtained 2 to 9.8 years prior to MM diagnosis were available. Using assays for monoclonal (M)-proteins (electrophoresis/ immunofixation) and kappa-lambda free light chains (FLCs), we determined longitudinally the prevalence of MGUS and characterized patterns of monoclonal immunoglobulin abnormalities prior to MM diagnosis. MGUS was present in 100.0% (87.2%-100.0%), 98.3% (90.8%-100.0%), 97.9% (88.9%-100.0%), 94.6% (81.8%-99.3%), 100.0% (86.3%-100.0%), 93.3% (68.1%-99.8%), and 82.4% (56.6%-96.2%) at 2, 3, 4, 5, 6, 7, and 8+ years prior to MM diagnosis, respectively. In approximately half the study population, the M-protein concentration and involved FLC-ratio levels showed a yearly increase prior to MM diagnosis. In the present study, an asymptomatic MGUS stage consistently preceded MM. Novel molecular markers are needed to better predict progression to MM in patients with MGUS.

Original languageEnglish (US)
Pages (from-to)5412-5417
Number of pages6
JournalBlood
Volume113
Issue number22
DOIs
StatePublished - 2009

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Monoclonal Gammopathy of Undetermined Significance
Multiple Myeloma
Prospective Studies
Electrophoresis
Immunoglobulins
Assays
Screening
Proteins
Plasmas
Light
Plasma Cells
Early Detection of Cancer
Ovarian Neoplasms
Population
Colorectal Neoplasms
Lung Neoplasms
Prostatic Neoplasms

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma : A prospective study. / Landgren, Ola; Kyle, Robert A.; Pfeiffer, Ruth M.; Katzmann, Jerry A.; Caporaso, Neil E.; Hayes, Richard B.; Dispenzieri, Angela; Kumar, Shaji K; Clark, Raynell J.; Baris, Dalsu; Hoover, Robert; Rajkumar, S Vincent.

In: Blood, Vol. 113, No. 22, 2009, p. 5412-5417.

Research output: Contribution to journalArticle

Landgren, O, Kyle, RA, Pfeiffer, RM, Katzmann, JA, Caporaso, NE, Hayes, RB, Dispenzieri, A, Kumar, SK, Clark, RJ, Baris, D, Hoover, R & Rajkumar, SV 2009, 'Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: A prospective study', Blood, vol. 113, no. 22, pp. 5412-5417. https://doi.org/10.1182/blood-2008-12-194241
Landgren, Ola ; Kyle, Robert A. ; Pfeiffer, Ruth M. ; Katzmann, Jerry A. ; Caporaso, Neil E. ; Hayes, Richard B. ; Dispenzieri, Angela ; Kumar, Shaji K ; Clark, Raynell J. ; Baris, Dalsu ; Hoover, Robert ; Rajkumar, S Vincent. / Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma : A prospective study. In: Blood. 2009 ; Vol. 113, No. 22. pp. 5412-5417.
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abstract = "Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma-cell proliferative disorder associated with a life-long risk of progression to multiple myeloma (MM). It is not known whether MM is always preceded by a premalignant asymptomatic MGUS stage. Among 77 469 healthy adults enrolled in the nationwide population-based prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we identified 71 subjects who developed MM during the course of the study in whom serially collected (up to 6) prediagnostic serum samples obtained 2 to 9.8 years prior to MM diagnosis were available. Using assays for monoclonal (M)-proteins (electrophoresis/ immunofixation) and kappa-lambda free light chains (FLCs), we determined longitudinally the prevalence of MGUS and characterized patterns of monoclonal immunoglobulin abnormalities prior to MM diagnosis. MGUS was present in 100.0{\%} (87.2{\%}-100.0{\%}), 98.3{\%} (90.8{\%}-100.0{\%}), 97.9{\%} (88.9{\%}-100.0{\%}), 94.6{\%} (81.8{\%}-99.3{\%}), 100.0{\%} (86.3{\%}-100.0{\%}), 93.3{\%} (68.1{\%}-99.8{\%}), and 82.4{\%} (56.6{\%}-96.2{\%}) at 2, 3, 4, 5, 6, 7, and 8+ years prior to MM diagnosis, respectively. In approximately half the study population, the M-protein concentration and involved FLC-ratio levels showed a yearly increase prior to MM diagnosis. In the present study, an asymptomatic MGUS stage consistently preceded MM. Novel molecular markers are needed to better predict progression to MM in patients with MGUS.",
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