Sensitivity and Accuracy of different diagnostic approaches for monoclonal proteins
Using currently available data Table 1 shows the detection rate for all patients with Multiple Myeloma, AL amyloidosis, Light Chain Multiple Myeloma and Nonsecretory Multiple Myeloma using different combinations of diagnostic tests.1,2,3,4,5,6
It is important to note that for Light Chain Multiple Myeloma, Freelite® detected 100% of patients when compared to SPE and UPE which detected only 90%.
An optimal pick up rate for all paraproteins can be achieved by simply performing SPE or CZE plus Freelite® without the need for a urine sample.
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Protocols
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% of Paraproteins detected
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*Myeloma
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AL
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LCMM
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NSMM
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SPE/CZE alone
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90
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50
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40 - 57
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0
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SPE/CZE, serum IFE
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95
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70
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75
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0
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SPE/CZE and UPE
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95
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75
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90
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0
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SPE/CZE, UPE serum and urine IFE
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97
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90
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95
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0
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Freelite® alone
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96
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98
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100
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68**
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SPE/CZE and Freelite®
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99
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98
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100
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68**
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SPE/CZE, Freelite® and serum IFE
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99
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98
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100
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68**
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*Myeloma is inclusive of samples from patients identified with Intact Immunoglobulin Multiple Myeloma, Light Chain Multiple Myeloma and Nonsecretory Multiple Myeloma.
**A further 4/28 patients with suppression of one or both free light chains were identified in addition to this 68% equaling 82%.1
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Guidelines for using Freelite®
Guidelines for using Freelite®A fully automated and precise result on serum is considered preferable but has not, until the availability of Freelite® assays, been achievable.
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The International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders7 now recommend the use of Freelite®. Key recommendations are:
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A recent report by Katzmann et al.8 recommends a simplification of the plasma cell dyscrasia diagnostic algorithm mentioned in current International Myeloma Working Group guidelines indicating that only serum protein electrophoresis (SPE) and Freelite® free light chain (FLC) tests, may be needed in many cases.
"...because of the small incremental sensitivity provided by urine studies and serum IFE, the use of PEL [SPE] plus FLC provides a simple and efficient initial diagnostic screen for the high-tumour-burden monoclonal gammopathies such as MM [multiple myeloma], WM and SMM [smouldering multiple myeloma]. Urine studies and serum IFE can be ordered more selectively."
Problems of current assays for free light chain detection in serum revolve around the lack of sensitivity of SPE and IFE.
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Kappa
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Lambda
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SPE
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500-2000 mg/L
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500-2000 mg/L
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IFE
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150-500 mg/L
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150-500 mg/L
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Freelite®
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0.3 mg/L
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0.5 mg/L
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Due to the sensitivity of historical serum methods, it used to be recommended to test a 24 hour urine sample for free light chains (Bence Jones Protein). However, serum is a superior medium for numerous reasons.
This kappa/lambda plot shows the number of samples that would be misclassified as negative using SPE and IFE, but are detected with Freelite® serum free light chain assays.
(pIgG - polyclonal hypergammaglobulinaemia)
Since normal FLC concentrations are considerably below the detection limit of all the electrophoresis methods, some patients will always be missed by these techniques.
Freelite® quantifies free light chains into the normal range, and is more sensitive than current diagnostic tests available for myeloma.
This data illustrates the value of high sensitivity Freelite® serum free light chain assays for monitoring patients with myeloma. For these patients, uring free light chain concentrations were too low for reliable quantification. However, serum free light chains could be measured at all times using Freelite.9
Alyanakian et al. concluded, "Immunonephelometric measurement of serum free light chains are a reliable method for follow up of patients with light chain secreting monoclonal gammopathies". Also that for cases featuring hardly measurable amounts of light chain in the urine "...the serum free light chain assay proved sensitive enough for correlation with clinical events."
Copyright 2004 Wiley. Used with permission from Alyanakian et al. American Journal of Hematology, Wiley Interscience. www.interscience.wiley.com
- Katzmann JA, et al. Screening panels for detection of monoclonal gammopathies. Clin Chem 2009; 55:1517-1522 Request your copy - code MKG535
- Lachmann HJ, 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; 122:78-85 Request your copy - code MKG200
- Abraham RS, et al. Correlation of serum immunoglobulin free light chain quantification with urinary Bence Jones protein in light chain myeloma. Clin Chem 2002; 48:65-667
- Bradwell AR, et al. Serum test for assessment of patients with Bence Jones myeloma. Lancet 2003; 361:489-491 Request your copy - code MKG189
- Drayson M, et al. Serum free light chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood 2001; 97:2900-2902 Request your copy - code MKG183
- Dispenzieri, et al. International Myeloma Working Group guidelines for serum-free chain analysis in multiple myeloma and related disorders. Leukemia 2009; 23:215-224 Request your copy - code MKG514
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) for Multiple Myeloma V.1.2011. © 2010 National Comprehensive Cancer Network, Inc. All rights reserved.
- Katzmann, et al. Screening Panels for Detection of Monoclonal Gammopathies. Clinical Chemistry 2009; 55:8:1517-1522 Request your copy - code MKG535
- Marie-Alexandra A, et al. Free Immunoglobulin Light-Chain Serum Levels in the Follow-up of Patients With Monoclonal Gammopathies: Correlation With 24-hr Urinary Light-Chain Excretion
Am J Hematology 2004; 75:246-248 Request your copy - code MKG222
