Contributions
Abstract: PB2172
Type: Publication Only
Background
Current criteria differentiating between monoclonal gammopathy of unknown significance (MGUS), smoldering multiple myeloma (SMM) and multiple myeloma (MM) are included in the IMWG guidelines published in 2003. Recently in 2014, the IMWG updated the criteria and revised the definition of multiple myeloma by adding a serum free light chain ratio (sFLC) of > 100 as a definition for multiple myeloma requiring treatment. At present, two commercial assays for sFLC quantification are available: The TBS Freelite assay and the Siemens N Latex FLC assay. The first is based on polyclonal antibodies directed against a variety of FLC epitopes. It may be run on a wide range of nephelometers as well as turbidimeters. The second method uses a probe mixture of monoclonal antibodies and runs exclusively on Siemens nephelometers.
Aims
Here, we present a prospective monocentric trial evaluating sFLC measurement and calculated kappa/lambda ratio with the N Latex FLC and the Freelite assays in patients with MGUS, SMM and MM either newly diagnosed (NDMM), or relapsed and refractory (RRMM).
Methods
Between Apr. and Aug. 2016, 40 patients were included into the clinical trial. Patients underwent routine clinical analysis for sFLC. The trial included 5 patients with MGUS and 35 patients with MM. 8 had SMM, 33 NDMM and 2 RRMM. The involved light chain was kappa in 23 and lambda in 17 cases. sFLC analysis was performed at study entry and for a maximum of 6 analyses during follow-up. All samples were analyzed for sFLC on a single Siemens BN II analyzer with Freelite reagents (The Binding Site) and with N Latex reagents (Siemens Healthcare Diagnostics). Clinical diagnoses matching submitted serum samples were retrieved from the patients’ medical file. For method comparison Passing Bablok correlation analysis after log/log transformation was performed.
Results
Based on their established reference ranges, sFLC results were classified in different groups to perform an interrater agreement analysis. Values for concordance between the N Latex FLC and the Freelite test for kappa FLC, lambda FLC and kappa/lambda ratio in the total patient population were 0.85, 0.73 and 0.93 showing a very good concordance above 0.81 for FLC kappa and FLC ratio and still a good concordance for FLC lambda. In the regression analysis, the Pearson correlation coefficient (r) showed an overall good correlation with r = 0.977 for kappa, r = 0.900 for lambda and r = 0.975 for kappa/lambda ratio, respectively.In 35 patients with NDMM either smoldering or symptomatic, 17 (49%) patients showed sFLC ratio > 100 and involved FLC > 100 mg/L in the Freelite test. 7/17 of those identified patients had a sFLC ratio > 100 in the N Latex FLC assay plus one further patient. Applying a cutoff of 50 for N Latex FLC ratio identified 4 additional patients.
Conclusion
sFLC analysis requires continuous awareness of analytical limitations. Concordance between the Freelite and N Latex FLC assays show overall good concordance, however in single cases large differences are observed especially in measurement of lambda FLC. As the sFLC ratio > 100 is implemented in the IMWG criteria defining MM disease requiring treatment physicians should be aware that this criterion might be solely rely on the method or the analyzer used for determination of sFLC values. This might lead to discrepant decisions in a proportion of NDMM patients. Therefore, IMWG guidelines for treatment of NDMM including patients solely showing sFLC ratio > 100 should be carefully revised.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Abstract: PB2172
Type: Publication Only
Background
Current criteria differentiating between monoclonal gammopathy of unknown significance (MGUS), smoldering multiple myeloma (SMM) and multiple myeloma (MM) are included in the IMWG guidelines published in 2003. Recently in 2014, the IMWG updated the criteria and revised the definition of multiple myeloma by adding a serum free light chain ratio (sFLC) of > 100 as a definition for multiple myeloma requiring treatment. At present, two commercial assays for sFLC quantification are available: The TBS Freelite assay and the Siemens N Latex FLC assay. The first is based on polyclonal antibodies directed against a variety of FLC epitopes. It may be run on a wide range of nephelometers as well as turbidimeters. The second method uses a probe mixture of monoclonal antibodies and runs exclusively on Siemens nephelometers.
Aims
Here, we present a prospective monocentric trial evaluating sFLC measurement and calculated kappa/lambda ratio with the N Latex FLC and the Freelite assays in patients with MGUS, SMM and MM either newly diagnosed (NDMM), or relapsed and refractory (RRMM).
Methods
Between Apr. and Aug. 2016, 40 patients were included into the clinical trial. Patients underwent routine clinical analysis for sFLC. The trial included 5 patients with MGUS and 35 patients with MM. 8 had SMM, 33 NDMM and 2 RRMM. The involved light chain was kappa in 23 and lambda in 17 cases. sFLC analysis was performed at study entry and for a maximum of 6 analyses during follow-up. All samples were analyzed for sFLC on a single Siemens BN II analyzer with Freelite reagents (The Binding Site) and with N Latex reagents (Siemens Healthcare Diagnostics). Clinical diagnoses matching submitted serum samples were retrieved from the patients’ medical file. For method comparison Passing Bablok correlation analysis after log/log transformation was performed.
Results
Based on their established reference ranges, sFLC results were classified in different groups to perform an interrater agreement analysis. Values for concordance between the N Latex FLC and the Freelite test for kappa FLC, lambda FLC and kappa/lambda ratio in the total patient population were 0.85, 0.73 and 0.93 showing a very good concordance above 0.81 for FLC kappa and FLC ratio and still a good concordance for FLC lambda. In the regression analysis, the Pearson correlation coefficient (r) showed an overall good correlation with r = 0.977 for kappa, r = 0.900 for lambda and r = 0.975 for kappa/lambda ratio, respectively.In 35 patients with NDMM either smoldering or symptomatic, 17 (49%) patients showed sFLC ratio > 100 and involved FLC > 100 mg/L in the Freelite test. 7/17 of those identified patients had a sFLC ratio > 100 in the N Latex FLC assay plus one further patient. Applying a cutoff of 50 for N Latex FLC ratio identified 4 additional patients.
Conclusion
sFLC analysis requires continuous awareness of analytical limitations. Concordance between the Freelite and N Latex FLC assays show overall good concordance, however in single cases large differences are observed especially in measurement of lambda FLC. As the sFLC ratio > 100 is implemented in the IMWG criteria defining MM disease requiring treatment physicians should be aware that this criterion might be solely rely on the method or the analyzer used for determination of sFLC values. This might lead to discrepant decisions in a proportion of NDMM patients. Therefore, IMWG guidelines for treatment of NDMM including patients solely showing sFLC ratio > 100 should be carefully revised.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical