Introduction

sFLC protein detection

Plasma cells are a type of white blood cell that helps the body fight infection. Free light chains (FLC) are proteins that are produced when plasma cells produce antibodies. Multiple Myeloma is a malignancy of the bone marrow plasma cells, where one cell starts to divide uncontrollably. As all the malignant cells are derived from the same original progenitor, the cells are described as monoclonal plasma cells. These monoclonal plasma cells secrete antibodies in the same way healthy plasma cells do, but since they come from the same plasma cell clone, they are described as monoclonal proteins. Monoclonal proteins may be intact immunoglobulins or free light chains. sFLC test measures the level of two types of free light chains, kappa (κ) and lambda (λ), in the serum and lithium heparin and EDTA plasma.1,2,3

The serum free light chain (sFLC) assay is a quantitative test used to detect the levels of free light chains in the plasma.

Why is it important?

The Freelite® quantitative assay for FLC is a sensitive and specific test that aids in diagnosis and monitoring of various plasma cell disorders

The disorders include Multiple Myeloma (MM), intact immunoglobulin Multiple Myeloma (IIMM), light chain Multiple Myeloma (LCMM), oligo- and non-secretory Multiple Myeloma. 4,5

It also aids in the diagnosis and monitoring of AL Amyloidosis and Waldenström’s macroglobulinaemia. When used to monitor these diseases, sFLC assays can help identify response to treatments, disease progression, and relapse. 3,4,6,7,8

Freelite® assays are both CE marked, and 510k cleared.

Guidelines for monitoring

Serum FLC measurements are recommended as an aid in diagnosis and monitoring of Multiple Myeloma by the International Myeloma Working Group (IMWG), and an involved/uninvolved FLC ratio (when the involved FLC is at least 100 mg/L) is one of the "biomarkers of malignancy" to define the presence of MM. Freelite® assays are mentioned by name in these guidelines as the assay used to determine the recommended value.*

The guidelines for monitoring MM also recommend that sFLCs should be used to assess response to treatment in patients, when serum M-protein is ˂10 g/L, and urine M-protein is ˂200 mg/24 hours.9

*The decision to act when any of the SLiM biomarkers of malignancy (Bone Marrow Plasma Cells, sFLC, MRI) are the only Myeloma Defining Event, is case dependent.

Freelite and Hevylite assays
The optimal combination for the management of monoclonal gammopathy patients
Investigating Multiple Myeloma
Can Serum Free Light Chain testing replace Urine Protein Electrophoresis?

There are several benefits of using the sFLC assay for monitoring

It is important to note that the serum free light chain assay is not diagnostic in isolation and should be used in conjunction with other tests and clinical evaluations to confirm diagnosis.1,2,3,7,8,14

Useful for monitoring of patients treated for MM or AL amyloidosis

It helps to determine if the treatment was successful in reducing the number of plasma cells producing free light chains2,3,4,5,11,12,13

Optimal patient management

By tracking sFLC levels over time, physicians can monitor disease progression, evaluate treatment effectiveness, identify light chain escape and early relapse, to make more informed clinical decisions.2,3,12

More convenient than conventional urine anlysis

sFLC assays are more sensitive and convenient than conventional urine analysis and can be used alongside intact immunoglobulin measurements to improve patient management1,3,5,6,7,8

Easy to perform

It can be performed easily in an outpatient setting. The test involves taking a blood sample from the patient, which is sent to a laboratory for quantitative analysis. Results are typically available within a few days.

Sensitive

The test is very sensitive and can detect very low levels of sFLCs even when conventional methods (SPEP, UPEP, IFE) are negative. This can help in early detection and allow for earlier treatment intervention with potentially fewer complications, which may lead to better patient outcomes3,10

 

Freelite is a registered trademark of The Binding Site Group Ltd (Birmingham, UK) in certain countries.

 


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Abbreviations and Acronyms
Definitions  
FLC

Free light chains

IFE

Immunofixation

IMWG

International myeloma working group

IIMM

Intact immunoglobulin multiple myeloma

LCMM

Light chain multiple myeloma

MM

Multiple myeloma

MGUS

Monoclonal gammopathy of undetermined significance

sFLC

Serum free light chains

SPEP

Serum protein electrophoresis

UPEP

urine protein electrophoresis

References
1. Tosi P, et al. Serum free light-chain assay for the detection and monitoring of multiple myeloma and related conditions. Ther Adv Hematol 2013; 4:37-41
2. Kumar S, et al. Serum immunoglobulin free light chain measurement in AL amyloidosis: prognostic value and correlations with clinical features. Blood 2010; 116:5126-5129
3. Yang Y, et al. Comparison of two serum free light chain assays for the diagnosis of primary plasma cell malignant proliferative disease. Health Science Reports 2019; 2:e113
4. Rajkumar SV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014; 15:e538-e548
5. Kumar S, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016; 17:e328-46
6. Rajkumar SV, et al. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Blood Rev 2007; 21:255-265
7. Korde N, et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies. Blood 2011; 117:5573-5581
8. Bradwell AR, et al. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem 2001; 47:673-680
9. Dejoie T, et al. Responses in multiple myeloma should be assigned according to serum, not urine, free light chain measurements. Leukemia 2019; 33:313-318
10. Katzmann JA, et al. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem 2002; 48:1437-1444
11. Mollee P. Current trends in the diagnosis, therapy and monitoring of the monoclonal gammopathies. Clin Biochem Rev 2009; 30:93-103
12. Rajkumar SV, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood 2005; 106:812-817
13. Comenzo RL, et al. Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis. Leukemia 2012; 26:2317-25
14. Kyle RA & Rajkumar SV. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Curr Hematol Malig Rep 2010; 5:62-69