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Serum Free Light Chain Assays—Their Role in Multiple Myeloma
US Hematology, 2007;1(1):24-7
Globally, multiple myeloma (MM) accounts for 0.8% of all cancer deaths, with a survival rate of 50% of those enrolled in clinical trials.1,2 It is the most common bone marrow cancer in Europe, with over 77,000 patients undergoing treatment at any one time.3 In the US, MM is the second most common haematological malignancy, affecting 4.4/100,000 people per year, with a male to female ratio of 1.4:1.4 The pre-malignant condition to MM – monoclonal gammopathy of undetermined significance (MGUS) – is present in approximately 3% of Caucasians over 50 years of age.5 Approximately 1% of MGUS patients will progress to MM or a related malignant condition each year.6 MGUS is defined by a monoclonal immunoglobulin (Ig) (M-protein) concentration of <30g/l, with the bone marrow containing less than 10% plasma cells and the absence of lytic bone lesions, anaemia, hypercalcaemia and renal insufficiency.7,8 To make a diagnosis of MGUS, laboratories have traditionally used serum protein electrophoresis (PEL) to detect the presence of M-protein and to characterise the type using immunofixation electrophoresis (IFE). However, 15–20% of MM patients have light chain MM (LCMM) and 3% have non-secretory MM (NSMM), which have small or undetectable amounts of measurable monoclonal protein in their serum with PEL.9–11 Highly sensitive serum free light chain (SFLC) assays are now available for clinical use; they allow quantification of free lambda (λ) and kappa (κ) chains. This new assay provides clinicians with an additional method of predicting prognosis of MGUS.
In patients with no measurable monoclonal protein in serum or urine using the standard PEL test, SFLC assays are helpful. Unlike IFE, the SFLC assay is quantitative and, therefore, is more precise. In some cases, the bands produced in electrophoresis are not well defined and it can often be difficult to determine whether they indicate a low level of M-protein in the serum or show an oligoclonal variation. In this situation, an additional testing system would be beneficial. SFLC assays use polyclonal antibodies to measure the level of unbound κ and λ light chains in the serum by nephelometry. Light chains produced by the myeloma cells are either κ or λ. The result of the production of one SFLC and not the other will cause an abnormal κ–λ ratio. Normally, the ratio range is 0.26–1.65; however, if the level of free κ rises abnormally, the ratio will be shifted above 1.65, and vice versa. The M-protein has traditionally been measured using protein electrophoresis and IFE of a 24-hour urine collection.
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- Barlogie B, Kyle RA, Anderson KC, et al., Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321, J Clin Oncol, 2006;24:929–36.
- International Agency for Research on Cancer, CancerMondial GLOBOCAN 2002 Database, available at: www-dep.iarc.fr/
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- Kyle RA, Therneau TM, Rajkumar SV, et al., A long-term study of prognosis in monoclonal gammopathy of undetermined significance, N Engl J Med, 2002;346:564–9.
- International Myeloma Working Group, Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group, Br J Haematol, 2003;121:749–57.
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- B. Rajkumar SV, Kyle RA, Multiple myeloma: diagnosis and treatment, Mayo Clin Proc, 2005;80:1371–82.
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- Lachmann HJ, Gallimore R, Gillmore JD, et al., Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy, Br J Haematol, 2003;122:78–84.
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- Bradwell AR, Carr-Smith HD, et al., Serum test for assessment of patients with Bence Jones myeloma, Lancet, 2003;361:489–91.
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- Abraham RS, Katzmann JA, Clark RC, et al., Quantitative analysis of serum free light chains. A new marker for the diagnostic evaluation of primary systemic amyloidosis, Am J Clin Pathol, 2003;119:274–8.
- Mead GP, Carr-Smith HD, Drayson MT, et al., Serum free light chains for monitoring multiple myeloma, Br J Haematol, 2004; 126:348–54.
- Mösbauer U, Ayuk F, Schieder H, et al., Monitoring serum free light chains in patients with multiple myeloma who achieved negative immunofixation after allogeneic stem cell transplantation, Haematologica, 2007;92:275–6.
- Dispenzieri A, Lacy MQ, Katzmann MQ, et al., Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation, Blood, 2006;107(8):3378–83.
- A Rajkumar SV, Kyle RA, Therneau TM, et al., Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance, Blood, 2005;106:812–17.
- Cesana C, Klersy C, Barbarano L, et al., Prognostic factors for malignant transformation in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma, J Clin Oncol, 2002;20:1625–34.