Kappa Free Light Chain Drift Prompts the Need for a New Upper Limit of Normal Free Light Chain Ratio to Avoid an Epidemic of Kappa Light Chain Monoclonal Gammopathy of Undermined Significance

Abstract Background Multiple laboratory tests are employed for detection of monoclonal proteins in patients and include serum protein electrophoresis (SPEP), immunofixation electrophoresis, free light chain (FLC) immunoassay, and mass spectrometry (Mass-Fix). Recently, reports on a drift in FLC quantitation results have been brought to light. Methods We studied a cohort of 16 887 patients whose sera were tested for a monoclonal protein by a FLC assay, serum protein electrophoresis, and Mass-Fix. This is a retrospective study designed to assess the impact of a drift on the performance of FLC ratio (rFLC) in groups of patients with and without detectable plasma cell disorders (PCDs). Results The results demonstrated that 63% of patients with monoclonal protein equal or higher than 2 g/L (by SPEP) had an abnormal rFLC (reference range 0.26–1.65). Conversely, 16% of patients with undetectable monoclonal protein by other methods (i.e., SPEP and Mass-Fix) who also had no record of treated PCD had an abnormal rFLC. In these cases, there was an imbalance in the number of kappa high rFLCs to lambda low rFLCs of 201 to 1. Conclusions The results of this study suggest decreased specificity of rFLC for a monoclonal kappa FLC in the 1.65 to 3.0 range.