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.
Serum Free Light Chain Assays—Their Role in Multiple Myeloma
US Hematology, 2007;1(1):24-7
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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/
- Ries LA, Melbert D, Krapcho M, (eds) et al., SEER Cancer Statistics Review, 1975-2004. Bethesda: National Cancer Institute, 2007. Available at: http://seer.cancer.gov/csr/1975_2004/
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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.
- Kyle RA, Monoclonal gammopathy of undetermined significance: natural history in 241 cases, Am J Med, 1978;64:814–26.
- B. Rajkumar SV, Kyle RA, Multiple myeloma: diagnosis and treatment, Mayo Clin Proc, 2005;80:1371–82.
- Drayson MT, Tang LX, Drew R et al., Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma, Blood, 2001;97:2900–2902.
- 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.
- Bradwell AR, Serum free light chain analysis, 3rd edn, Birmingham, UK: The Binding Site Ltd., 2005;13–21.
- Bradwell AR, Carr-Smith HD, et al., Serum test for assessment of patients with Bence Jones myeloma, Lancet, 2003;361:489–91.
- Abraham RS, Clark RJ, Bryant SC, et al., Correlation of serum immunoglobulin free light chain quantitation with urine Bence Jones protein in light chain myeloma [Technical Brief], Clin Chem, 2002;48:655–7.
- Katzmann JA, Abraham RS, Dispenzieri A, et al., Diagnostic performance of quantitative and free light chain assays in clinical practice, Clin Chem, 2005;51:878–81.
- 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.