Serum Free Light Chain Levels in Asymptomatic Myeloma.
Authors: Augustson Bradley M. , Reid Steven D. , Mead Graham P. , Drayson Mark T. , Child J. Anthony , Bradwell Arthur R. 
Published: October 2019

Abstract
Introduction: Patients with asymptomatic myeloma fulfil two of the diagnostic criteria for myeloma having more than 10% bone marrow plasma cells and an M protein of greater than 30g/l, but they are asymptomatic with no evidence of end organ or tissue damage. The median time to disease progression is 12–32 months. These patients do not require treatment but do require monitoring for progression to symptomatic myeloma. Predicting progression of asymptomatic myeloma would be of clinical benefit to optimise monitoring and initiate treatment prior to substantial end organ damage. However monoclonal spike, plasma cell labelling index, bone marrow plasmacytosis, immunoparesis and the presence of Bence Jones protein have limited value in predicting progression. Abnormal levels of serum free light chains are present in 95% of all multiple myeloma patients and have clinical benefit in diagnosis and monitoring of disease. In monoclonal gammopathy of undetermined significance (MGUS) 60% of patients have abnormal serum free light chain ratios and are an independent risk factor for progression to myeloma. The aim of this study was to examine the serum of asymptomatic patients for serum free light chains at diagnosis and to determine if they are predictive of disease progression.
Methods: Archived presentation sera were studied from forty three asymptomatic myeloma patients who had been registered into United Kingdom Medical Research Council trials (1980 – 2002). Archived presentation sera were assayed for serum free light chains using the serum free light chain assay on an Olympus AU400 analyzer. Times to progression for those with abnormal versus normal serum free light chain ratios were compared. Times to progression were examined by Kaplan-Meier survival curves and log-rank sum statistical analysis.
Results: Abnormal serum free light ratios were present in 36/43 (84%) of asymptomatic myeloma patients at the time of diagnosis and the remaining 7 patients had normal ratios. The median follow-up time for all 43 patients was 2807 days. Six patients with a normal kappa/lambda ratio had a median time to progression of 1323 days. In contrast, 26 patients with abnormal serum free kappa/lambda ratios had a median time to progression of 713 days. Ten patients who had an abnormal kappa/lambda ratio had not progressed at the time of follow-up. Although the median time to progression of patients with normal serum free light chain ratios was greater than those with abnormal ratios, this did not reach statistical significance (p<0.13).
Conclusions: In summary, 84% of asymptomatic myeloma patients have an abnormal kappa/lambda ratio at diagnosis, in comparison with 95% of multiple myeloma and 60 % of (MGUS) patients. Furthermore, our data suggest that those with normal serum free light chain ratio may progress more slowly than those with abnormal ratios. Due to the small number of patients in this study, this did not reach statistical significance. In the spectrum of malignancy from MGUS to asymptomatic and symptomatic myeloma serum free light chain levels have an increasing frequency of abnormality and are associated with increased risk of progression to symptomatic myeloma.