Clinical recommendations for the measurement of serum free light chains and the emerging role of heavy/light chain pair analysis in the management of monoclonal gammopathies: When and how to use it?

Protein and immunofixation electrophoresis are the laboratory backbone assays for testing multiple myeloma (MM) and related plasma cell proliferative diseases. The secreted monoclonal proteins act as serological tumor markers, and the electrophoretic assays identify monoclonal proteins for diagnosis as well as quantitate these markers for monitoring clinical course and response to therapy. However these techniques present limitations, especially in patients with nonsecretory MM, light chain MM, and amyloid light chain amyloidosis. Freelite, a nephelometric/turbidimetric serum assay for the measurement of serum free light chains, has improved the management of patients with monoclonal gammopathies and has been included in international myeloma working group guidelines for the screening, prognostic, monitoring and as response criteria. Recently, a new assay, Hevylite; , was also approved by Food and Drug Administration for the monitoring of IgA and IgG MM. It allows the quantification of each immunoglobulin subtype (i.e., IgGκ, IgGλ, IgAκ, IgAλ), enables analysis of specific involved/monoclonal and uninvolved/polyclonal immunoglobulins heavy/light chain pairs, which produce immunoglobulin heavy/light chain ratios and may improve sensitivity for identifying residual disease and relapse in some patients. Together, these assays are important tools which will help us to achieve the correct diagnostic and follow-up of B cell dyscrasias