An assay for the measurement of serum free light chains (sFLCs) was developed in the early 2000s. Since then an explosion of literature advocating its use in a number of scenarios from diagnosis to monitoring of plasma cell dyscrasias has appeared. This assay is now increasingly requested in clinical practice and has diagnostic, monitoring and prognostic value. Despite the wealth of literature, hitherto there was no published guideline defining the use of sFLCs in the diagnosis and management of plasma cell dyscrasias.

This guideline provides a concise overview of the development and use of the assay, stressing the importance of the κ/λ FLC ratio, rather than elevations in κ and λ FLC that could be the result of immune stimulation or decreased renal clearance. Problems of polymerization of light chains and antigen excess of the assay are also highlighted.

The use of sFLCs in three clinical areas – diagnosis, prognosis and response to treatment – is examined. With respect to diagnosis, studies have concentrated on a subset of patients positive for Bence Jones protein. However, the guideline also recommends the use of sFLCs in combination with serum electrophoresis and immunofixation as a screen for all monoclonal plasma proliferative disorders, except AL amyloidosis. In terms of prognosis, it is recommended that sFLCs should be measured at diagnosis for all patients with monoclonal gammopathy of undetermined significance, smouldering or active multiple myeloma, solitary plasmacytoma and AL amyloidosis. The potential of this assay in serial measurement is problematic due to non-linear dilution and lot-to-lot variation. Therefore, recommendations for assessing response have only been made in AL amyloidosis and oligosecretory disease.