B-075 Evaluation of patients with monoclonal gammopathy of undetermined significance using Optilite Freelite assays

Abstract

Abstract Background Monoclonal gammopathy of undetermined significance (MGUS) is a pre-malignant disorder with a progression risk to multiple myeloma of 1% per year. Patients with MGUS may produce monoclonal intact immunoglobulins (Ig) and/or free light chains (FLC). The International Myeloma Working Group (IMWG) recommendations for the use of FLC measurements in MGUS are to establish the diagnosis of light chain only MGUS (LC-MGUS) and further to risk-stratify newly diagnosed MGUS. Once identified, MGUS is longitudinally monitored at intervals dependent on the risk of transformation. The IMWG recommends serum protein electrophoresis (SPEP) for monitoring of known MGUS with intact Ig, however others have published benefits of additionally monitoring with FLC. In this study, we evaluated the diagnostic sensitivity and specificity of the Optilite® Freelite® Kappa Free Kit and the Optilite Freelite Lambda Free Kit (The Binding Site, part of Thermo Fisher Scientific) in patients with MGUS, and the monitoring performance of Freelite results measured in serial samples from patients with clinically stable and progressive MGUS. Methods Serum samples from 234 patients with clinically diagnosed MGUS and 140 disease controls, taken at single time points, and serial samples (≥3) from 49 patients with MGUS were tested with the Freelite assays. Intact M-protein presence and isotype was confirmed in MGUS samples with immunofixation electrophoresis (IFE). In patients clinically diagnosed with LC-MGUS, the presence of detectable M protein on IFE was not required. The disease control cohort (non-MGUS) had disorders commonly associated with elevated polyclonal immunoglobulins (e.g autoimmune, liver, and renal diseases), confirmed by total IgG and/or IgA and/or IgM results and the absence of M-protein by IFE. Patients represented a diverse population from both European and US sources. Results The overall diagnostic sensitivity of the Optilite Freelite assays was 59.4%, calculated as the frequency of abnormal free light chain ratio (rFLC) in intact immunoglobulin MGUS, and abnormal rFLC with concurrent elevated involved FLC level in LC-MGUS. The diagnostic sensitivity was: 58.0% in non-IgM MGUS, 41.7% in IgM MGUS, 66.7% in biclonal MGUS and 100% in LC-MGUS. In intact (IgG/IgA/IgM) kappa MGUS, the diagnostic sensitivity was 67.5%, versus 41.5% in intact (IgG/IgA/IgM) lambda MGUS. The diagnostic specificity was 86.4%. In the 49 patients with serial samples, concentrations of involved FLC were stable in 93.3% of patients with clinically stable MGUS, whereas in patients with clinically progressive MGUS an increasing trend was seen in 50% of cases. Conclusions These results demonstrate that the Optilite Freelite Kappa and Lambda assays produce clinically relevant results that are useful in the evaluation of MGUS.