Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Apr;27(4):941-6.
doi: 10.1038/leu.2012.296. Epub 2012 Oct 16.

Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma

J T Larsen  1 , S K Kumar, A Dispenzieri, R A Kyle, J A Katzmann, S V Rajkumar
Affiliations

Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma

J T Larsen et al. Leukemia. 2013 Apr.

Abstract

A markedly elevated serum free light chain (FLC) ratio may serve as a biomarker for malignant transformation in high-risk smoldering multiple myeloma (SMM) and identify patients who are at imminent risk of progression. We retrospectively studied the predictive value of the serum (FLC) assay in 586 patients with SMM diagnosed between 1970 to 2010. A serum involved/uninvolved FLC ratio ≥ 100 was used to define high-risk SMM, which included 15% (n=90) of the total cohort. Receiver operating characteristics analysis determined the optimal FLC ratio cut-point to predict progression to symptomatic multiple myeloma (MM) within 2 years of diagnosis, which resulted in a specificity of 97% and sensitivity of 16%. Fifty-six percent of patients developed progressive disease during median follow-up of 52 months, but this increased to 98% in the subgroup of patients with FLC ratio ≥ 100. The median time to progression in the FLC ratio ≥ 100 group was 15 months versus 55 months in the FLC <100 group (P<0.0001). The risk of progression to MM within the first 2 years in patients with an FLC ratio ≥ 100 was 72%; the risk of progression to MM or light chain amyloidosis in 2 years was 79%. We conclude that a high FLC ratio ≥ 100 is a predictor of imminent progression in SMM, and such patients may be considered candidates for early treatment intervention.

PubMed Disclaimer

Figures

Figure 1
Figure 1
ROC curve demonstrating the sensitivity and specificity of the initial involved/uninvolved FLC ratio for progression to symptomatic multiple myeloma within 24 months of SMM diagnosis. The FLC ratio cut-point of ≥100 has a specificity of 96.7% and sensitivity of 15.8%.
Figure 2
Figure 2
TTP to symptomatic multiple myeloma from initial involved/uninvolved FLC ratio of ≥100 versus a ratio of <100. Median TTP was 15 months in the FLC ratio ≥100 group compared with 55 months in the FLC ratio <100 group (P<0.0001). At 24 months, 72% of patients with FLC ratio ≥100 had progressed to MM versus 28% of patients with FLC ratio <100.
See this image and copyright information in PMC

References

    1. Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010;24:1121–1127. - PMC - PubMed
    1. Group TIMW Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003;121:749–757. - PubMed
    1. Rajkumar SV, Gertz MA, Lacy MQ, Dispenzieri A, Fonseca R, Geyer SM, et al. Thalidomide as initial therapy for early-stage myeloma. Leukemia. 2003;17:775–779. - PubMed
    1. Barlogie B, van Rhee F, Shaughnessy JD, Jr., Epstein J, Yaccoby S, Pineda-Roman M, et al. Seven-year median time to progression with thalidomide for smoldering myeloma: partial response identifies subset requiring earlier salvage therapy for symptomatic disease. Blood. 2008;112:3122–3125. - PMC - PubMed
    1. Musto P, Petrucci MT, Bringhen S, Guglielmelli T, Caravita T, Bongarzoni V, et al. A multicenter, randomized clinical trial comparing zoledronic acid versus observation in patients with asymptomatic myeloma. Cancer. 2008;113:1588–1595. - PubMed

Publication types

Substances