Serum Free Light Chain Analysis and Urine Immunofixation Electrophoresis in Patients with Multiple Myeloma

Abstract

Purpose: Retrospective studies have shown that immunoassays measuring free light chains (FLC) in serum are useful for diagnosis and monitoring of multiple myeloma. This study prospectively evaluates the use of FLC assays and, for the first time, investigates the relationship between serum FLC concentrations and the presence and detectability of BenceJones (BJ) proteins in the urine. Patients and Methods: Three hundred seventy-eight paired samples of serum and urine were tested from 82 patients during the course of their disease. The sensitivities of serum FLC analysis and urine immunofixation electrophoresis (IFE) in detecting monoclonal FLC were compared. Serum FLC concentrations required for producing BJ proteins detected by IFE were determined. Results: Abnormal FLC were present in 54% of serum samples compared with 25% by urine tests. In abnormal serum samples for n or E, the sensitivity of IFE to detect the respective BJ proteins in urine were 51% and 35% and the median serum FLC concentrations required to produce detectable BJ proteins were 113 and 278 mg/L. Renal excretions of monoclonal FLC increased with serum concentrations, but excretions significantly decreased at high serum concentrations combined with renal dysfunction. Conclusion: Serum FLC assays are significantly more sensitive for detecting monoclonal FLC than urine IFE analysis. They also have the advantage of FLC quantification and are more reliable for monitoring disease course and response to treatment.

International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders

“…Its major deficiency in addressing this question is that the population tested included patients with positive urine immunofixation studies; the chosen selection criteria answered the question they posed, but increased the likelihood of a positive serum FLC assay as the median amounts of serum FLCs required to produce overflow proteinuria has been measured at 113 mg/l for k (range, 7-39 500 mg/l) and 278 mg/l for l (range, 6-710 mg/l). 22 There are several papers that show that the addition of FLC to serum PEL or capillary zone electrophoresis increases the sensitivity of these tests, which is not surprising because they only detect monoclonal proteins large enough to be seen through a normal or polyclonal background. PEL and capillary zone electrophoresis should not be considered sufficient testing when contemplating a diagnosis of plasma cell disorder.…”

“…Consistently, however, it has been shown that there is not a strong correlation between serum FLC and measurement or urine FLC by 24 h protein electrophoresis. 3,12,15,22,40 When evaluating the performance of changes of serum FLC and of urinary M-spikes over time, there is a relationship to the changes, but to date, no one has shown high correlation coefficients.…”

Serum free light chain analysis

“…In these patients, several studies have found that the serum FLC assay is more sensitive than 24-hr urine collection for BJ protein as detected by immunofixation assay, particularly in the setting of relapsed disease [8,9]. A prospective study of 82 patients with paired serum FLC and urine BJ proteins found that abnormal FLC were present in the serum in 54% of cases compared with 25% by urine BJ protein [10]. These findings have led some to conclude that when serum FLC testing is available, a 24-hr urine collection is no longer required for the measurement of light chain production [9].…”

Screening for M-proteinemia: serum protein electrophoresis and free light chains compared

“…In addition, the FLC assay is not only more sensitive than SPE and IFE for the detection of light chain disease, but also in revealing amyloidosis (13) and non-secretory myeloma (10). Most published studies have used the serum FLC assays in addition to SPE and IFE (14)(15)(16)(17)(18)(19)(20), or in combination with clinical information (21). Interestingly, after reading the paper by Abadie and Bankson (22), one might conclude that the FLC assay also could be used for screening of monoclonal gammopathy since the FLC assay had better positive and negative predictive values compared to SPE.…”