A new retrospective analysis has highlighted the crucial role of serum-free light chain (sFLC) measurement in providing earlier and more reliable indicators of disease response and progression, even in patients already monitored through traditional electrophoresis testing.
Serum-free light chain response assessment
The study analysed data from 839 patients with measurable multiple myeloma (MM), all assessed using both sFLC and serum or urine electrophoresis. Researchers found a strong association between sFLC and electrophoretic responses during initial therapy and at the point of best response (p<0.001). Percentage changes in serial differences of FLC (dFLC) closely matched trends seen with urine M-protein, demonstrating strong correlations (r 0.55–0.79, p<0.001).
Importantly, sFLC identified treatment responses earlier than electrophoresis by an average of 1.1 months (95% CI 1.06–1.17). Patients who achieved at least a partial response by sFLC after two induction cycles were significantly more likely to show corresponding improvements on electrophoresis (odds ratio 9.33, p<0.001). Despite the earlier detection advantage, progression-free survival (PFS) rates were similar across methods when comparing very good partial response (VGPR) identified through sFLC, serum protein electrophoresis (sPEP), or urine protein electrophoresis (uPEP) (p=0.538).
Improving accuracy in disease monitoring
Among patients experiencing disease progression, 12% showed sFLC as the only detectable tumour marker at the start of second-line treatment. Interestingly, these patients exhibited significantly better overall survival after relapse compared with those whose progression was detected by urine M-protein, whether or not accompanied by sFLC changes (hazard ratio 1.87, 95% CI 1.07–3.27, p=0.03).
These findings suggest that serial sFLC testing provides an independent and sensitive measure for tracking both response and progression in multiple myeloma. The study supports adopting sFLC as a core component of disease monitoring, potentially replacing cumbersome 24-hour urine collection methods. Broader incorporation of sFLC into clinical protocols could streamline assessments and ensure earlier detection of treatment efficacy and relapse.
Reference
Askari E et al. Value of serum-free light chain measurements in response and progression assessment in multiple myeloma with monoclonal protein measurable by electrophoresis. Blood Cancer Journal. 2025;15:133.







