Serum free light chain analysis in the diagnosis and management of multiple myeloma and related conditions

Abstract

The serum free light chain (FLC) assay is an important tool in the management of patients with monoclonal gammopathies. MEDLINE^®, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews from January 2000 through July 2013, were used as data sources. The available evidence is rather weak. For screening of multiple myeloma and related conditions, the association of the FLC assay with the traditional serum tests avoids urine study. Screening for immunoglobulin light-chain (AL) amyloidosis or other rare syndromes requires the urine examination. FLC measurement is used in the assessment of the risk of progression of precursor diseases to overt myeloma, and for risk stratification in solitary plasmacytoma, multiple myeloma and AL amyloidosis. In patients with oligosecretory myeloma and AL amyloidosis, the quantification of FLC is essential for monitoring and categorization of response to therapy. Further studies with improved design are warranted to strengthen the available evidence.

Keywords::

• Bence-Jones protein
• monoclonal gammopathies
• oligosecretory myeloma
• screening
• urinalysis

Financial & competing interests disclosure

This work was supported by the Ministry of Research and University (2007AESFX2-003), and Associazione Italiana per la Ricerca sul Cancro Special Program 5x1000 Molecular Clinical Oncology (grant 9965). G Merlini has received honoraria from Millennium Takeda, Pfizer, The Binding Site and Siemens. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The free light chain (FLC) assay had a great impact on the care of monoclonal gammopathies improving the screening, the risk assessment and the evaluation of response to therapy.

• It has revolutionized the care of diseases caused by the systemic proteotoxic effect exerted by light chains, such as AL amyloidosis, light chain deposition disease and monoclonal gammopathies of renal significance.

• The quantification of serum FLC may also contribute in deciding the best timing for starting treatment in asymptomatic myeloma with the aim of reducing morbidity and extend survival.

• The clinician should be aware of the analytical pitfalls of the FLC assay in order to properly use the test and to correctly implement the proposed recommendations.

• Guidelines for the optimal use of FLC assay have been developed and should be used in the appropriate clinical setting, always in combination with clinical judgement.

• The introduction of novel assays for the measurement of FLC, while enriches the field offering alternatives, demands rigorous comparative studies and clinical validation with accurate definition of outcomes.

Notes