Freelite™
Serum Free Light Chain Assays
An aid to the diagnosis of:
Light Chain (Bence Jones) Multiple Myeloma (LCMM) Nonsecretory Multiple Myeloma (NSMM) AL amyloidosis Light Chain Deposition Disease (LCDD) Waldenströms Macroglobulinaemia An aid to monitoring treatment and disease in: Intact Immunoglobulin Multiple Myeloma (IIMM) Light Chain Multiple Myeloma Nonsecretory Multiple Myeloma AL amyloidosis Light Chain Deposition Disease Waldenströms Macroglobulinaemia Interpretation of Serum Free Light Chain
Results
λ Ratio Sector Kappa Lambda κ/λ
1 Normal Normal serum Normal BM suppression without MG 3 High Monoclonal Gammopathy 4 Low 2 Normal Normal Interpretation Low 5 Low Normal 6 Normal High Low Low High 9 10 Normal Normal serum High Monoclonal Gammopathy High Normal plg or renal impairment Low Monoclonal Gammopathy Low High Monoclonal Gammopathy Normal High Monoclonal Gammopathy Normal plg or renal impairment Low 12 13 15 High 16 17 Monoclonal Gammopathy
Normal 11 14 Normal serum Low 7 8 Normal High Normal 18 High 19 Low MG with renal impairment Without bone marrow (BM) suppression With bone marrow (BM) suppression MG = Monoclonal Gammopathy pIg = Polyclonal Immunoglobulin Sectors refer to areas of the kappa/lambda plot Kappa/Lambda Plot low normal high high λ Free Light Chains (mg/L) 1000 100 normal 10 low 1 1 10 100 κ Free Light Chains (mg/L) Normal sera κ LCMM λ LCMM 1000 IIMM Renal impairment High pIgG NSMM AL amyloidosis Serum kappa and lambda concentrations in a selection of clinical conditions. Patients are categorised according to serum free light chain concentrations and κ/λ ratios. Diagonal lines separate monoclonal from polyclonal diseases. pIgG ­ polyclonal hypergammaglobulinaemia Sector numbers refer to table opposite. Freelite results should be considered under the following categories and investigated appropriately: 1. Normal samples. Serum κ, λ and κ/λ ratio are all within the normal ranges. If accompanying serum electrophoretic tests are normal it is most unlikely that the patient has a monoclonal gammopathy. λ ratios. Support the diagnosis of a monoclonal 2. Abnormal κ/λ
gammopathy and require an appropriate tissue biopsy. Borderline elevated κ/λ ratios occur with renal impairment and may require appropriate renal function tests. 3. Low concentrations of κ, λ or both. Indicate bone marrow function impairment. λ ratio. May 4. Elevated concentrations of both κ and λ with a normal κ/λ
be due to the following: Renal impairment (common) Over­production of polyclonal FLCs from inflammatory conditions (common) Biclonal gammopathies of different FLC types (rare) λ ratio. 5. Elevated concentrations of both κ and λ with an abnormal κ/λ
Suggest a combination of monoclonal gammopathy and renal impairment. Freelite Reference Range Normal Adult Serum Mean Median Concentration Concentration 95 Percentile Range Free Kappa 8.36 (mg/L) 7.30 (mg/L) 3.30­19.40 (mg/L) Free Lambda 13.43 (mg/L) 12.40 (mg/L) 5.71­26.30 (mg/L) Mean Median Total range 0.63 0.60 0.26­1.65 Kappa/Lambda ratio Serum Reference Intervals and Diagnostic Ranges for Free κ
and Free λ Immunoglobulin Light Chains: Relative Sensitivity
for Detection of Monoclonal Light Chains.
Katzmann et al. Clin Chem 2002;48:1437­1444.
Monitoring Response AL amyloidosis ­ Haematological response criteria Definition of Organ Involvement and Treatment Response in
Immunoglobulin Light Chain Amyloidosis (AL): A Consensus
Opinion From The 10th International Symposium on Amyloid
and Amyloidosis.
Gertz et al. American Journal of Hematology 2005; 79:319­328
Monoclonal Gammopathies Patients can be monitored serially using the light chain levels and the ratio. Recently the International uniform response criteria has indicated using the difference in values between the tumour involved light chain and the uninvolved light chain. These criteria provide standardisation for clinical outcomes in trials. Sections relevant to serum free light chain (FLC) measurements: Response Response Criteria Stringent Complete Response (sCR) Normal serum FLC ratio Measurable disease* Abnormal serum FLC ratio and involved serum FLC > 100 mg/L Partial Response* > 50% decrease in the difference between involved and uninvolved FLC levels Progressive disease* Increase >25% from baseline in the difference between involved and uninvolved Free Light
Chain levels and the absolute increase >100mg/L * where immeasurable by SPE, 24h UPE or quantitative immunoglobulin analysis International uniform response criteria for multiple myeloma
BGM Durie et al. Leukemia 2006;20(9):1467­1473
Note: The guidelines in this document are recommendations only. Final interpretation of results of the Freelite assays should be determined by clinicians caring for each patient following review of all available clinical information and current diagnostic and management guidelines. These guidelines are subject to revision and updates. U.S.A. & Canada:
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