Clinical Significance Of Serum Free Light Chain Immunoassay In Multiple Myeloma

Monoclonal free light chains (FLC) (traditionally termed Bence Jones proteins) are homogeneous populations of kappa (κ) or lambda (λ) immunoglobulin light chain molecules produced by malignant clones of B-cells. They are important tumor markers for identifying and monitoring patients with light chain multiple myeloma (LCMM) and light chain amyloid disease (AL).FlLC are normally identified in urine, using protein electrophoresis (PE) or immunofixation electrophoresis (IFE).However, these techniques are time-consuming, relatively insensitive and can be inaccurate. An alternative to urine assessment is to measure FLC concentrations in serum. In a series of recent studies using highly sensitive immunoassays, it was shown that FLC measurements in serum were preferable to the traditional urine electrophoresis tests for the diagnosis of patients with nonsecretory myeloma (NSMM) , AL and LCMM . Similar benefits, in terms of sensitivity and precision of results, were also observed when monitoring these patients.In the first section of the paper, we evaluated sFLC diagnostic performance in NSMM. All sFLC clinical test results generated in 2006 were abstracted from the NSMM patients serum which were frozen . The FLC assay (FREELITETM; The Binding Site Ltd.) was performed on a Hitachi modular P automated nephelometer. This assay consists of two separate measurements: one to quantifyκFLCs and the other to quantifyλFLCs. Results Using sensitive, automated immunoassays, increased concentrations of eitherκorλfree light chains (and abnormalκ/λratios) were detected in the sera of 6 of 9 patients with NSMM and 2 patient with renal impairment had elevated bothκFLC andλFLC concentration.The remaining 3 sera had normal sFLC. Conclusion Quantification of free light chains in serum should prove useful for the different diagnosis of many patients with NSMM.In the second section of the paper, we explore the clinical significance of serum free light chains (sFLC) measurements in IgG multiple myeloma(MM). sFLC and IgG in 30 patients with IgG MM measured by nephelometry at baseline ,early stage(days 7-10) and late stage (days 28-35) in one circle chemotherapy, respectively. Patients responses were assessed by the decreased levels of sFLC and IgG at early and late stage and twenty one patients who had measurable disease followed up by the second circle chemotherapy. Twenty three out of 30 patients had abnormal elevated sFLC and ratio of freeκ/λ. Twenty one out of 30 patients had abnormal total light chain levels and ratio of totalκ/λ.Both of sFLC and total light chain in patients with IgG MM were abnormal in five newly diagnosed MM patients and 6 patients whose disease status were progressive diseases. The Pearson correlation coefficient between sFLC and total light chain levels was 0.64 at baseline .The sensibility and specificity of response of PR (partial remission ) were 100% and 92.3% according to the sFLC assessment criteria at the early stage meanwhile the sensibility of response of PR were 25% according to the IgG assessment criteria. The sensibility and specificity of response of PD were 100% and 93.8% according to the sFLC criteria at the late stage meanwhile the sensibility of response of PD according to IgG criteria were zero. Conclusion More than 75% patients with IgG MM have abnormal sFLC concentrations and ratio of freeκ/λ. Serum FLC concentrations respond more quickly to treatment than IgG and provide early evidence of PD.