Redefining light-chain smoldering multiple myeloma : prevalence and progression risk
(2026) In Leukemia- Abstract
- Smoldering multiple myeloma (SMM) is a precursor to multiple myeloma (MM) and present in 0.5% of the population over 40 years old [1, 2]. In 10–20% of MM patients, the clonal BMPC do not produce intact M proteins but only free light chains (FLC) [3, 4]. This subgroup termed light-chain MM and well-characterized, but light-chain SMM is not clearly defined.
Historically, monoclonal FLC were detected by urine protein electrophoresis (UPEP), but methods of detecting FLC in serum have become widely available and are used to infer the presence of monoclonal FLC. The higher sensitivity of serum FLC analysis and the convenience of a single blood sample over a 24-h urine collection have made this the preferred method for evaluating... (More) - Smoldering multiple myeloma (SMM) is a precursor to multiple myeloma (MM) and present in 0.5% of the population over 40 years old [1, 2]. In 10–20% of MM patients, the clonal BMPC do not produce intact M proteins but only free light chains (FLC) [3, 4]. This subgroup termed light-chain MM and well-characterized, but light-chain SMM is not clearly defined.
Historically, monoclonal FLC were detected by urine protein electrophoresis (UPEP), but methods of detecting FLC in serum have become widely available and are used to infer the presence of monoclonal FLC. The higher sensitivity of serum FLC analysis and the convenience of a single blood sample over a 24-h urine collection have made this the preferred method for evaluating monoclonal gammopathies in clinical practice [5,6,7].
The only prior study on light-chain SMM, a single-center retrospective analysis, defined the diagnosis based on urinary monoclonal FLC (≥0.5 g/24 h) and/or >10% BMPC, in the absence of intact serum M protein and end-organ damage [8]. However, this study lacked FLC measurements in many cases, and bone marrow evaluation was missing in up to 40%. In addition, some individuals (27 of 73 tested) would now meet criteria for MM due to an FLC ratio >100. Thus, a refined diagnostic criteria and characterization of light-chain SMM is needed.
The aim of this study was to define and characterize light-chain SMM using FLC analysis and bone marrow sampling within the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study. In addition, to externally validate the proposed definition in a population-based clinical cohort in Denmark (the Danish Lymphoid-lineage Cancer Research; DALY-CARE) and to estimate the progression risk.
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- Leukemia
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- Nature Publishing Group
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- scopus:105044227387
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- 10.1038/s41375-026-03028-8
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@article{69c8e716-dfff-4c52-bf30-2cff3c9c7d7a,
abstract = {{Smoldering multiple myeloma (SMM) is a precursor to multiple myeloma (MM) and present in 0.5% of the population over 40 years old [1, 2]. In 10–20% of MM patients, the clonal BMPC do not produce intact M proteins but only free light chains (FLC) [3, 4]. This subgroup termed light-chain MM and well-characterized, but light-chain SMM is not clearly defined.<br/><br/>Historically, monoclonal FLC were detected by urine protein electrophoresis (UPEP), but methods of detecting FLC in serum have become widely available and are used to infer the presence of monoclonal FLC. The higher sensitivity of serum FLC analysis and the convenience of a single blood sample over a 24-h urine collection have made this the preferred method for evaluating monoclonal gammopathies in clinical practice [5,6,7].<br/><br/>The only prior study on light-chain SMM, a single-center retrospective analysis, defined the diagnosis based on urinary monoclonal FLC (≥0.5 g/24 h) and/or >10% BMPC, in the absence of intact serum M protein and end-organ damage [8]. However, this study lacked FLC measurements in many cases, and bone marrow evaluation was missing in up to 40%. In addition, some individuals (27 of 73 tested) would now meet criteria for MM due to an FLC ratio >100. Thus, a refined diagnostic criteria and characterization of light-chain SMM is needed.<br/><br/>The aim of this study was to define and characterize light-chain SMM using FLC analysis and bone marrow sampling within the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study. In addition, to externally validate the proposed definition in a population-based clinical cohort in Denmark (the Danish Lymphoid-lineage Cancer Research; DALY-CARE) and to estimate the progression risk.<br/><br/>}},
author = {{Maeng, Cecilie Velsoe and Thorsteinsdóttir, Sigrún and Óskarsson, Jón Þórir and Rögnvaldsson, Sæmundur and Long, Thórir Einarsson and Brieghel, Christian and Andersen, Morten Nørgaard and Ólafsson, Andri and Þórðardóttir, Ásdís R and Viðarsson, Brynjar and Önundarson, Páll T and Agnarsson, Bjarni A and Sigurðardóttir, Margrét and Þorsteinsdóttir, Ingunn and Ólafsson, Ísleifur and Eyþórsson, Elías and Jónsson, Ásbjörn and Harding, Stephen and Landgren, Ola and Love, Thorvardur Jon and Grønbæk, Kirsten and Niemann, Carsten U and Kristinsson, Sigurður Y}},
issn = {{1476-5551}},
language = {{eng}},
month = {{07}},
publisher = {{Nature Publishing Group}},
series = {{Leukemia}},
title = {{Redefining light-chain smoldering multiple myeloma : prevalence and progression risk}},
url = {{http://dx.doi.org/10.1038/s41375-026-03028-8}},
doi = {{10.1038/s41375-026-03028-8}},
year = {{2026}},
}