Suppression of uninvolved immunoglobulins defined by heavy/light chain pair suppression is a risk factor for progression of MGUS

J. A. Katzmann, R. Clark, R. A. Kyle, D. R. Larson, T. M. Therneau, L. J. Melton, J. T. Benson, C. L. Colby, A. Dispenzieri, O. Landgren, S. Kumar, A. R. Bradwell, J. R. Cerhan, S. V. Rajkumar

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

We hypothesized that the suppression of uninvolved immunoglobulin in monoclonal gammopathy of undetermined significance (MGUS) as detected by suppression of the isotype-specific heavy and light chain (HLC-pair suppression) increases the risk of progression to malignancy. This approach required quantitation of individual heavy/light chains (for example, IgGλ in IgGκ MGUS patients). Of 1384 MGUS patients from Southeastern Minnesota seen at the Mayo Clinic from 1960 to 1994, baseline serum samples obtained within 30 days of diagnosis were available in 999 persons. We identified HLC-pair suppression in 27% of MGUS patient samples compared with 11% of patients with suppression of uninvolved IgG, IgA or IgM. HLC-pair suppression was a significant risk factor for progression (hazard ratio (HR), 2.3; 95% confidence interval (CI) 1.5-3.7; P<0.001). On multivariate analysis, HLC-pair suppression was an independent risk factor for progression to malignancy in combination with serum M-spike size, heavy chain isotype and free light chain ratio (HR, 1.8; 95% CI, 1.1-3.00; P=0.018). The finding that HLC-pair suppression predicts progression in MGUS and occurs several years before malignant transformation has implications for myeloma biology.

Original languageEnglish (US)
Pages (from-to)208-212
Number of pages5
JournalLeukemia
Volume27
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • MGUS
  • heavy/light
  • multiple myeloma
  • prognosis
  • suppression

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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