Serum-free light-chains (SFLC) instead of urine protein electrophoresis (UPEP) for monitoring light-chain multiple myeloma (LCMM)

Background: Response and follow-up criteria in multiple myeloma (MM) are still based on the protein electrophoretic (PEP) quantification of the monoclonal protein (MP) in serum (s) and / or urine (u). Monitoring MP by urine (u) PEP has a very low sensitivity for evaluating variations of small amounts of MP. Since 2001, serum free light-chain assays (sFLC) are available, with demonstrated clinical utility. Dejoie et al. have recently reported the usefulness of sFLC for evaluating response in LCMM. Aims: In this work, we try to validate the use of sFLC assay in the context of GEM/PETHEMA clinical trials in order to evaluate the responses and its advantages in comparison to standard quantification of MP by PEP in serum (s) and -mainly- urine (u) after treatment, given the usual difficulties to collect and adequately perform urine studies in the usual clinical praxis. Methods: We included 169 patients with Bence Jones (BJ) MM with measurable urine disease who have being treated according to GEM/PETHEMA clinical trials (GEM05menos65, GEM05MAS65, GEM2010MAS65 and GEM2012 menos65). Serum FLC assays (FreeliteR, The Binding Site, Birmingham, UK) were performed on an automated nephelometer (BNII, Dade Behring / Siemens, Marburg, Germany). The electrophoretic study of the monoclonal component (CM) was performed by capillary electrophoresis (V8, Helena Biosciences Europe), and immunofixation was performed for the Ig, γ, ? and ? chains (SAS-3 and SAS-4, Helena Bioscience Europe). Results: From a total of 169 patients with LCMM (93 Bence Jones kappa / 76 Bence Jones Lambda), 146 (86%) had FLC data at diagnosis, with 139/146 (95%) evaluable by FLCs [involved sFLC ≥100)]. In addition, 68 of the 169 patients also had detectable MP in serum and 7 of the 169 had non-evaluable MP in urine (MP <0.200 g/24h). We studied the correlation of both techniques' MP quantification results (uPEP vs isFLC) and we observed a low correlation (Pearson's r 0.293, p =0.003), that should be partly explained by the low profitability and subjectivity of the electrophoresis technique for quantifying paraprotein in urine. [Figure 1A]. The concordance between the classification of the response by uPEP / immunofixation (IF) and by FLCs (Kappa Index=0.425 p <0.0001) was moderate. The normalization of the sFLC ratio (r) was reached in 35/98 (36%) patients after treatment, associated to a lower risk of progression (normal vs abnormal sFLCr: PFS 60 vs 39 months, p =0.038) but without impact in overall survival in our series. We also observed that an absolute value of isFLC greater than 50mg/L after treatment was associated with an increased risk of progression, regardless of the response achieved (PFS 60 vs 28 months, p<0.0001). [Figure 1B]. (Figure presented). Summary/Conclusions: There is an acceptable agreement between both methods for response evaluation. The sFLC assays provide a greater sensitivity than the urine protein electrophoresis for monitoring low levels of disease in certain cases with measurable disease at diagnosis (isFLC ≥100) being useful for its follow-up, and also provide prognostic value as a predictor of progression.