Evaluating the clinical utility of serum free light chain measurement and reference change value in monitoring monoclonal gammopathy

Background: Serum free light chain (sFLC) measurement is highly sensitive for detecting low levels of immunoglobulins but has limited ability to distinguish between polyclonal and monoclonal increases. This study retrospectively evaluated the clinical utility of interpreting sFLC results using reference change values (RCVs) rather than conventional reference intervals (RIs) for detecting disease relapse in patients with multiple myeloma-related plasma cell disorders, where appropriate.

Methods: A total of 254 paired immunofixation electrophoresis (IFE) and sFLC results obtained from 143 patients were evaluated, including repeated measurements from 50 patients. Immunofixation electrophoresis was used as the comparative reference method. Serum kappa, lambda, and κ/λ ratio results were interpreted using population-based reference intervals, and RCVs for sFLC measurements were calculated. Sensitivity and specificity for detecting disease-related changes during follow-up were compared between RI-based and RCV-based interpretation.

Results: The calculated RCVs for increases and decreases in kappa and lambda light chains ranged from 27% to 40%. During follow-up, nine patients achieved remission, one experienced relapse, and disease status remained stable in 40 patients. Interpretation of the κ/λ ratio using reference intervals yielded a sensitivity of 50% and a specificity of 78%, whereas RCV-based evaluation of sFLC results showed a sensitivity of 80% and a specificity of 50%.

Conclusions: Given the limited sensitivity of κ/λ ratio interpretation based solely on reference intervals, its usefulness for longitudinal disease monitoring may be restricted. Application of RCV-based interpretation to serial sFLC measurements may enhance the detection of clinically meaningful disease-related changes during follow-up, particularly in patients with low-level or stable sFLC concentrations.