Comparison of three different serum-free light-chain assays\u2014implications on diagnostic and therapeutic monitoring of multiple myeloma

Aneta Schieferdecker,Sebastian Hörber,Britta Besemer,Andreas Peter,Carsten Bokemeyer,Katja Weisel,Monika Ums

doi:10.1038/s41408-019-0267-8

Abstract

The measurement of serum-free light chains (FLC) is standard of care in the diagnosis and management of multiple myeloma (MM). The revised international myeloma working group (IMWG) implemented the involved FLC/noninvolved FLC (iFLC/niFLC) ratio as a biomarker for MM requiring treatment. Recently, a new definition of high-risk smoldering MM (SMM) including iFLC/niFLC ratio was published. These recommendations were solely based on a single assay method (Freelite assay). Today, two additional assays, N Latex FLC and ELISA-based Sebia FLC, are available. Here, we report on a single-center-study comparing results of all three different assays for FLC correlation and its potential implications for diagnostic and clinical use. In total, 187 samples from 47 MM patients were examined, and determination of FLC was performed. Comparison analyses showed similar FLC results for Sebia FLC and N Latex FLC assay with markedly lower absolute values for κ/λ ratio compared with Freelite. Values of λ FLC exhibited high variability. The ratio of iFLC/niFLC showed significant discrepancies among these assays. Our data demonstrate that the three available assays may result in markedly discrepant results, and should not be used interchangeably to monitor patients. Furthermore, modifications of the assay-specific diagnostic (iFLC/niFLC) thresholds for SMM and MM are recommended.

Highlights

Serum-free light chains (FLC) are important biomarkers for the diagnosis and management of smoldering multiple myeloma (SMM), multiple myeloma (MM), and other plasma cell disorders, such as monoclonal gammopathy of undetermined significance (MGUS), lightchain amyloidosis (AL-amyloidosis), and light-chain deposition disease (LCDD)[1,2,3,4,5,6].In MM patients, the determination of FLC is used in the initial diagnostic assessment and during follow-up monitoring
In the absence of a measurable serum and urine M-protein, response assessment is based on the percentage decrease of difference between involved and noninvolved FLC7
In LCDD and AL-amyloidosis, response assessment relies on absolute and percentage decrease of difference between involved and noninvolved FLC4–6

Summary

Introduction

Serum-free light chains (FLC) are important biomarkers for the diagnosis and management of smoldering multiple myeloma (SMM), multiple myeloma (MM), and other plasma cell disorders, such as monoclonal gammopathy of undetermined significance (MGUS), lightchain amyloidosis (AL-amyloidosis), and light-chain deposition disease (LCDD)[1,2,3,4,5,6].In MM patients, the determination of FLC is used in the initial diagnostic assessment and during follow-up monitoring. Determination of stringent complete response (sCR) is defined by complete response (negative immunofixation in serum and urine, plasma cells in the bone marrow < 5%) with normalized kappa/lambda ratio (κ/λ ratio)[3]. In the absence of a measurable serum and urine M-protein, response assessment is based on the percentage decrease of difference between involved and noninvolved FLC (partial response is defined as dFLC decrease > 50%)[7]. In LCDD and AL-amyloidosis, response assessment relies on absolute and percentage decrease of difference between involved and noninvolved FLC (partial response is defined as dFLC decrease > 50% and very good partial response as dFLC < 40 mg/l)[4,5,6].

Methods

Results

Conclusion