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Revised free light chain reference intervals enhance risk stratification in monoclonal gammopathy of undetermined significance and reduce overdiagnosis

Maeng, Cecilie Velsoe ; Rögnvaldsson, Sæmundur ; Einarsson Long, Thórir LU ; Brieghel, Christian ; Hermansen, Emil ; Niemann, Carsten Utoft ; Grønbæk, Kirsten ; Kristinsson, Sigurður Yngvi and Thorsteinsdóttir, Sigrún (2025) In Blood Cancer Journal 15(1).
Abstract

The free light chain (FLC) ratio is a critical part of risk stratification for monoclonal gammopathy of undetermined significance (MGUS). Recently, revised FLC reference intervals developed using the iStopMM cohort, accounting for age and renal function, have reduced the rate of abnormal findings. Here, we examine the implications of the revision in an independent Danish MGUS cohort. Of 6993 MGUS individuals, 2641 had an abnormal FLC ratio by the original intervals, of whom 844 (32%) were reclassified as normal using the revised intervals. Reclassified individuals had no significantly increased risk of progression compared to those with a normal FLC ratio (hazard ratio (HR): 1.07, 95% confidence interval (CI) 0.74-1.57). Those with an... (More)

The free light chain (FLC) ratio is a critical part of risk stratification for monoclonal gammopathy of undetermined significance (MGUS). Recently, revised FLC reference intervals developed using the iStopMM cohort, accounting for age and renal function, have reduced the rate of abnormal findings. Here, we examine the implications of the revision in an independent Danish MGUS cohort. Of 6993 MGUS individuals, 2641 had an abnormal FLC ratio by the original intervals, of whom 844 (32%) were reclassified as normal using the revised intervals. Reclassified individuals had no significantly increased risk of progression compared to those with a normal FLC ratio (hazard ratio (HR): 1.07, 95% confidence interval (CI) 0.74-1.57). Those with an abnormal FLC ratio by the revised reference intervals had an increased risk of progression (HR 2.23, 95% CI 1.79-2.78). Using the revised reference intervals, 490 individuals (16%) were reclassified to low-risk from a higher risk group. These individuals had a similar progression risk compared to others in the low-risk group. The findings validate the revised FLC reference intervals, enhancing prognostic accuracy and improving risk stratification to accurately identify MGUS individuals at risk of progression while reducing unnecessary classifications as high-risk.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Monoclonal Gammopathy of Undetermined Significance/diagnosis, Female, Male, Aged, Middle Aged, Immunoglobulin Light Chains/blood, Risk Assessment, Aged, 80 and over, Adult, Reference Values, Disease Progression, Medical Overuse/prevention & control, Denmark/epidemiology
in
Blood Cancer Journal
volume
15
issue
1
article number
80
publisher
Nature Publishing Group
external identifiers
  • scopus:105003762979
  • pmid:40295472
ISSN
2044-5385
DOI
10.1038/s41408-025-01289-7
language
English
LU publication?
yes
additional info
© 2025. The Author(s).
id
4c982845-1adc-44ea-864f-4a9a6ee3c5f1
date added to LUP
2025-04-30 10:36:37
date last changed
2025-07-05 04:05:09
@article{4c982845-1adc-44ea-864f-4a9a6ee3c5f1,
  abstract     = {{<p>The free light chain (FLC) ratio is a critical part of risk stratification for monoclonal gammopathy of undetermined significance (MGUS). Recently, revised FLC reference intervals developed using the iStopMM cohort, accounting for age and renal function, have reduced the rate of abnormal findings. Here, we examine the implications of the revision in an independent Danish MGUS cohort. Of 6993 MGUS individuals, 2641 had an abnormal FLC ratio by the original intervals, of whom 844 (32%) were reclassified as normal using the revised intervals. Reclassified individuals had no significantly increased risk of progression compared to those with a normal FLC ratio (hazard ratio (HR): 1.07, 95% confidence interval (CI) 0.74-1.57). Those with an abnormal FLC ratio by the revised reference intervals had an increased risk of progression (HR 2.23, 95% CI 1.79-2.78). Using the revised reference intervals, 490 individuals (16%) were reclassified to low-risk from a higher risk group. These individuals had a similar progression risk compared to others in the low-risk group. The findings validate the revised FLC reference intervals, enhancing prognostic accuracy and improving risk stratification to accurately identify MGUS individuals at risk of progression while reducing unnecessary classifications as high-risk.</p>}},
  author       = {{Maeng, Cecilie Velsoe and Rögnvaldsson, Sæmundur and Einarsson Long, Thórir and Brieghel, Christian and Hermansen, Emil and Niemann, Carsten Utoft and Grønbæk, Kirsten and Kristinsson, Sigurður Yngvi and Thorsteinsdóttir, Sigrún}},
  issn         = {{2044-5385}},
  keywords     = {{Humans; Monoclonal Gammopathy of Undetermined Significance/diagnosis; Female; Male; Aged; Middle Aged; Immunoglobulin Light Chains/blood; Risk Assessment; Aged, 80 and over; Adult; Reference Values; Disease Progression; Medical Overuse/prevention & control; Denmark/epidemiology}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Blood Cancer Journal}},
  title        = {{Revised free light chain reference intervals enhance risk stratification in monoclonal gammopathy of undetermined significance and reduce overdiagnosis}},
  url          = {{http://dx.doi.org/10.1038/s41408-025-01289-7}},
  doi          = {{10.1038/s41408-025-01289-7}},
  volume       = {{15}},
  year         = {{2025}},
}