From the Guidelines
Free light chains (FLCs) are small protein fragments produced by plasma cells in the bone marrow that can be measured in the blood to diagnose and monitor conditions like multiple myeloma, amyloidosis, and other plasma cell disorders. According to the NCCN clinical practice guidelines in oncology 1, the serum free light-chain (FLC) assay is a valuable tool in screening for these conditions, as well as in prognostication and quantitative monitoring of patients with light chain amyloidosis and light chain myeloma.
Key Points
- FLCs are components of antibodies (immunoglobulins) that normally exist as paired heavy and light chains 1
- Measuring FLCs in blood is important for diagnosing and monitoring plasma cell disorders 1
- The serum FLC assay yields high sensitivity while screening for multiple myeloma (MM) and related plasma cell disorders 1
- The FLC ratio is required for documenting stringent complete response (CR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria 1
Clinical Implications
- Elevated levels or an abnormal ratio between kappa and lambda chains can indicate disease 1
- Free light chain testing provides valuable information about disease activity and treatment response in patients with plasma cell disorders 1
- The serum FLC assay cannot replace the 24-hour UPEP for monitoring patients with measurable urinary M-protein and can also be affected by renal function 1
From the Research
Definition and Measurement of Free Light Chains
- Free light chains (FLCs) are immunoglobulin light chains that are not bound to heavy chains, and their measurement is important in the diagnosis and management of plasma cell disorders 2, 3, 4, 5, 6.
- The serum FLC assay measures levels of free kappa and lambda immunoglobulin light chains, and it has been shown to be sensitive and specific for detecting FLC diseases such as primary systemic amyloidosis, light chain deposition disease, and nonsecretory multiple myeloma 2, 3.
Clinical Applications of Free Light Chains
- The FLC assay has several clinical applications, including screening for multiple myeloma and related disorders, baseline measurement for prognostic value, and quantitative monitoring of patients with oligosecretory plasma cell disorders 3.
- Serial FLC measurements have been shown to be useful in monitoring patients with light chain amyloidosis and oligosecretory myeloma, and they may reduce the need for frequent bone marrow biopsies 3.
- FLCs are also useful as a diagnostic and therapeutic marker in patients with primary systemic AL amyloidosis, and their levels can be used to monitor response to chemotherapy 5.
Diagnostic Sensitivity of Free Light Chains
- The diagnostic sensitivity of FLCs has been evaluated in several studies, and they have been shown to be a sensitive and specific marker for monoclonal gammopathies 2, 3, 6.
- The combination of serum immunofixation electrophoresis and serum FLC assay has been shown to detect an abnormal result in 99% of patients with AL amyloidosis 2.
- FLCs have also been shown to be useful in the diagnosis of light chain deposition disease and nonsecretory multiple myeloma 2, 4.