Performance of Free Light Chain reagents in the Dutch External Quality Assessment programme over the past 14 years

Serum free light chain measurements (sFLC) play a key role in the diagnosis and management of patients with monoclonal gammopathies. To obtain a realistic impression of between-method performance and agreement of sFLC analysis in The Netherlands, we studied results of 37 laboratories participating in 56 rounds of the Dutch External Quality Assessment (EQA) programme in the past fourteen years. Satisfactory overall method-specific between-laboratory precision was observed for both The Binding Site Freelite (mean CV κFLC 23.3% and λFLC 19.5%) and Siemens N Latex FLC (κFLC 10.8% and λFLC 15.2%). Within-laboratory precision as tested in seven EQA samples that were repeatedly sent to all participants was adequate for both Freelite (mean CV κFLC 16.4% and λFLC 15.6%) and N Latex FLC (κFLC 9.8% and λFLC 19.6%). Method comparison and Bland-Altman analyses demonstrated a systematic bias between both methods over the entire range of sFLC testing. In general, Freelite results were higher compared to N Latex FLC (relative median bias: κFLC +29.7% and λFLC +37.0%). Clinical concordance of the FLC ratio interpretation was high between both methods (88%). Especially at high FLC concentrations, strong method-specific differences were observed in individual EQA samples which also resulted in discordances in reported FLC ratio around clinically relevant cut-off points. Method-stratified sFLC reporting in EQA programmes creates awareness that current sFLC assays are not equivalent, hampering the application of universal diagnostic, prognostic, or response criteria. Such EQA may also provide opportunities for monitoring the success of future sFLC standardisation initiatives.