What is the purpose of the serum free light chain (FLC) lab test?

Purpose of Serum Free Light Chain (FLC) Lab Test

The serum free light chain (FLC) assay is primarily used to screen for, diagnose, and monitor multiple myeloma and related plasma cell disorders, offering high sensitivity for detecting abnormal plasma cell populations and monitoring disease response, particularly in light chain myeloma and nonsecretory myeloma. 1

Diagnostic Applications

• The FLC assay, when used alongside serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (SIFE), provides high sensitivity for screening multiple myeloma and related plasma cell disorders 1, 2
• Testing helps establish clonality of plasma cells by measuring kappa and lambda light chains and calculating their ratio, which is essential for diagnosing multiple myeloma and related disorders 2, 3
• The serum FLC assay is particularly valuable for diagnosing light chain myeloma, nonsecretory myeloma, and amyloidosis, where conventional testing might miss the disease 2, 4
• An abnormal FLC ratio (kappa/lambda) indicates restricted light chain expression, which becomes apparent when the monoclonal population exceeds 30% of polyclonal cells 2

Prognostic Value

• The serum FLC assay has prognostic value in various plasma cell disorders, including monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, active myeloma, and immunoglobulin light chain amyloidosis 1
• Abnormal FLC ratios help identify patients with higher risk of progression from precursor conditions like MGUS to active multiple myeloma 2
• The FLC ratio is required for documenting stringent complete response (sCR) according to the International Myeloma Working Group Uniform Response Criteria 1

Monitoring Disease Activity

• The serum FLC assay allows for quantitative monitoring of patients with light chain amyloidosis and oligosecretory myeloma 1
• FLC concentrations respond more rapidly to treatment than intact immunoglobulins due to their shorter half-life (2-6 hours vs. 21 days for IgG), providing earlier indication of treatment response 4
• The test is useful for monitoring disease response and progression in patients with nonsecretory myeloma, where conventional testing shows no measurable protein 1

Technical Considerations and Limitations

• The FLC assay cannot replace the 24-hour urine protein electrophoresis (UPEP) for monitoring patients with measurable urinary M-proteins 1
• After quantifying the myeloma or M-protein, it's crucial to use the same test for serial studies to ensure accurate relative quantification 1, 3
• Renal impairment can cause decreased clearance of both kappa and lambda free light chains, potentially leading to false elevations 2, 3
• Different FLC assays may provide inequivalent absolute results, making it important to use the same method for patient follow-up 5, 6

Clinical Applications Beyond Multiple Myeloma

• The FLC assay is valuable for diagnosing monoclonal gammopathy of renal significance (MGRS), where monoclonal immunoglobulins cause kidney damage 2
• It helps identify light chain escape, where disease evolves to become oligosecretory, nonsecretory, or light chain-only disease 2
• In AL amyloidosis, the FLC assay has shown higher sensitivity (91%) compared to serum immunofixation (69%) and urine immunofixation (83%) 7

Common Pitfalls and Best Practices

• Urine-free light chain assay should not be performed; instead, 24-hour urine collection for electrophoresis and immunofixation is recommended 2
• A 24-hour urine collection cannot be replaced by a morning urine sample for accurate assessment 2
• For patients with renal impairment due to light chain cast nephropathy, prompt initiation of appropriate therapy is recommended to decrease production of nephrotoxic clonal immunoglobulin 2