What is the FLC Ratio?
The free light chain (FLC) ratio is the kappa/lambda ratio calculated from serum free light chain measurements, with a normal reference range of 0.26-1.65, used to detect clonality and assess prognosis in plasma cell disorders including multiple myeloma. 1
Definition and Measurement
The serum FLC assay independently measures unbound kappa (κ) and lambda (λ) immunoglobulin light chains, then calculates their ratio (κ/λ). 1, 2 An abnormal ratio indicates clonality: a high ratio (>1.65) suggests a kappa clone, while a low ratio (<0.26) indicates a lambda clone. 1
Critical Consideration in Renal Impairment
In patients with impaired renal function, the normal FLC ratio range expands significantly to 0.34-3.10 in severe renal impairment (CKD stage 5 or greater), because free light chains are normally cleared by the kidneys. 1 This is particularly important in your older patient with suspected multiple myeloma and renal dysfunction, as standard reference ranges will lead to misinterpretation. 1
Assay-Specific Differences
- Two major assays exist (FreeLite and N Latex) with mathematically inconvertible results 1
- The N Latex assay is less affected by renal impairment than FreeLite 1
- The same assay must be used consistently for serial monitoring of any individual patient 1
Clinical Applications in Multiple Myeloma
Diagnostic Utility
- The serum FLC assay combined with SPEP and SIFE provides high sensitivity for screening multiple myeloma and related plasma cell disorders 1
- Essential for detecting light chain-only disease and oligosecretory myeloma 1
- Required for documenting stringent complete response per International Myeloma Working Group criteria 1
Prognostic Significance
Extreme FLC ratio abnormalities predict worse outcomes: 1, 3
- In smoldering myeloma: FLC ratio <0.125 or >8 independently predicts progression, with median time to progression of 1.9 years when combined with other high-risk features 1, 4
- In newly diagnosed symptomatic myeloma: FLC ratio <0.03 or >32 predicts inferior survival (30 vs 39 months median survival) 3
- FLC ratio ≥100 identifies ultra-high-risk smoldering myeloma with 72% risk of progression within 2 years and median time to progression of only 15 months 5
Risk Stratification Model
For smoldering myeloma, assign 1 point for each: 1
- Bone marrow plasma cells ≥10%
- Serum M-protein ≥3 g/dL
- FLC ratio <0.125 or >8
Median times to progression: 10 years (1 factor), 5.1 years (2 factors), 1.9 years (3 factors). 1
Important Limitations
- Cannot replace 24-hour urine protein electrophoresis for monitoring patients with measurable urinary M-proteins 1
- Affected by renal function, requiring adjusted interpretation 1
- Serum immunofixation may be more helpful than FLC assays in diseases with intact monoclonal immunoglobulin (e.g., PGNMID) 1
Recommended Workup in Your Clinical Scenario
For an older patient with suspected myeloma and renal impairment: 1, 6
- Obtain serum FLC assay with kappa/lambda ratio calculation
- Perform serum and urine immunofixation to definitively identify monoclonal protein
- Complete renal function assessment with creatinine clearance
- 24-hour urine collection for protein electrophoresis and immunofixation
- Interpret FLC ratio using renal-adjusted reference ranges (0.34-3.10 for severe CKD) 1
- Document which FLC assay is used for future serial monitoring 1