Clinical Comparison of the Freelite and N-Latex Serum Free Light Chain (FLC) Assays in the Diagnosis and Monitoring of AL Amyloidosis

We compared a novel assay for FLC quantitation based on monoclonal antibodies (N Latex) to the established polyclonal antibody-based assay (Freelite) in AL amyloidosis.

62 diagnostic samples from patients with AL amyloidosis were analysed, 32 of which also had a post-treatment sample. Serum FLC concentration was measured by Freelite (The Binding Site, UK) and N Latex (Siemens, Germany) immunoassays on a BNII nephelometer. Serum and urine immunofixation electrophoresis (IFE) was performed on Hydrasys gel systems (Sebia, France).

In the diagnostic samples: for AL of kappa type (n=18), the median involved FLC (iFLC) was significantly lower by the N Latex assay (289 vs 667mg/L, p=0. 0002) whereas in AL of lambda type (n=44) the values were similar (148 vs 161mg/L, p=0. 84). Measurable disease has recently been redefined as a difference between the involved and uninvolved FLC (dFLC) of > 50mg/L. By these criteria, 82% AL would be measurable by the N Latex assay compared to 89% by the Freelite assay. In terms of the diagnostic sensitivity, the FLC ratio was normal in 21% and 15% of patients by the N Latex assay and Freelite assays, respectively. The combination of serum and urine IFE with either FLC assay, however, allowed identification of the amyloidogenic clone in 98% producing comparable sensitivity for both methods.

For the 32 patients with monitoring samples the median overall survival was 50 months. The median reduction in dFLC was 40% for the N Latex assay and 61% for the Freelite assay (p=0. 03). This led to some differences in assigning response categories. In patients with measurable disease (dFLC>50mg/L), a partial remission (dFLC reduction >50%) predicted overall survival by the N Latex (n=25, 2yr OS 82% vs 27%, p=0. 0015) and Freelite assays (n=29, 2yr OS 75% vs 36%, p=0. 02).

There are significant differences between iFLC as measured by the N Latex and Freelite assays, but overall the two assays have similar diagnostic sensitivity when used in combination with serum and urine IFE. In the monitoring context, preliminary data suggests that disease response as assessed by the N Latex FLC assay predicts overall survival. Because of the likely widespread introduction of this assay and the differences in absolute levels of iFLC measured by these assays, consensus criteria may need to be reconsidered.

No relevant conflicts of interest to declare.