Evaluation of the siemens N Latex free light chain assay and comparison to Binding Site Freelite™ assay

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S113-S113
Author(s):  
H Lin
Keyword(s):  
Multiple Myeloma ◽  
Binding Site ◽  
Light Chain ◽  
Polyclonal Antibodies ◽  
Pearson Correlation ◽  
Method Comparison ◽  
Free Light Chain ◽  
Analytical Performance ◽  
Clinical Samples ◽  
Serum Free Light Chain

Abstract Introduction/Objective The International Myeloma Working Group (IMWG) guidelines include serum free light chain (sFLC) level and κ/λ ratio as excellent indicators of clonality. The Binding Site Freelite ™ was the first FDA approved assay for quantitative measurement of sFLC, the assay was based on a mixture of polyclonal antibodies directed against a variety of FLC epitopes. The Siemens N-Latex assay employs a probe mixture of mouse monoclonal antibodies. Both assays can be run on nephelometers. We assessed the analytical performance of the N-Latex assays and compared it with the Freelite™ assays. Methods/Case Report Analytical accuracy, precision, reproducibility and linearity were evaluated according to the regulatory standards. Method comparison was performed with 220 clinical samples for statistic correlation and clinical concordance analysis. Results (if a Case Study enter NA) The N-Latex FLC κ and λ assays had coefficient variation of 1-5% with-in run and 3-8% between run precision. Accuracy was verified using assayed controls in the duration of 21 days. Within analytical measuring range, almost perfect linearity was achieved for both κ and λ FLC assays. In comparison study to Freelite™ with 220 clinical samples, good agreement in classification was observed for κ, λ and κ/λ ratio (Cohen’s κ 0.73, 0.82 and 0.87). Pearson correlation analysis showed correlation coefficient value r >0.90 for all the analytes. Conclusion The N-Latex FLC assay has good analytical performance, did not exhibit gross antigen excess and can be used in clinical practice. However, it showed markedly lower absolute values for κ/λ ratio compared with Freelite™. Our data demonstrated that although good clinical concordance between N-Latex and Freelite™ FLC assays was achieved, the absolute values from the two assay are not interchangeable. Further studies in modification of the assay-specific diagnostic (involved FLC/non-involved FLC) thresholds for smoldering multiple myeloma (SMM) and multiple myeloma (MM) are needed.

Serum Free Light Chain and Serum Heavy / Light Chain Ratios Are Independently Prognostic in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4880-4880
Author(s):  
Efstathios Koulieris ◽  
Stephen Harding ◽  
Marie-Christine Kyrtsonis ◽  
Caroline Bradley ◽  
Mark T Drayson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Binding Site ◽  
Prognostic Marker ◽  
Light Chain ◽  
Prognostic Indicator ◽  
Free Light Chain ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Site Group ◽  
Serum Igg

Abstract Abstract 4880 Serum free light chain ratios (FLCr) are important prognostic markers in B cell malignancies and their measurement has recently been included in multiple myeloma (MM) international guidelines. In contrast, serum IgG and IgA concentrations are not prognostic in MM. Novel immunoassays have been developed which target the specific conformational, junctional epitopes between the heavy and light chains of the immunoglobulin making it possible to measure Ig'kappa and Ig'lambda and produce an Ig'kappa /Ig'lambda ratio. Here we describe the use of FLCr and heavy/light chain ratios (HLCr) to predict survival in MM patients. Archived sera from a historic MRC and a more recent Velcade, Adriamycin, dexamethazone (PAD) MM trail were utilised and the data combined using each study as a categorical variable. 85 MRC and 73 PAD samples were analysed retrospectively using serum free light chain and serum heavy / light chain nephelometric assays (The Binding Site Group). Kaplan Meier curves and Cox regression analysis were constructed comparing the upper quartile to the lower three quartiles for involved intact immunoglobulin, FLC, HLC and FLC + HLC. All analysis was completed using SPSS v14.0. FLCr and HLCr values were not correlated (Pearson's = -0.037 p=0.66). There was no significant difference in survival when comparing the lower three quartiles and upper quartile of the involved intact immunoglobulin (Hazard Ratio [HR]=1.16: p=0.585). However, comparison of the upper quartile to the lower three quartiles did reveal significant differences in survival times for FLCr (HR=2.16: p=0.003), HLCr (HR=1.94: p=0.01) and FLCr+HLCr (HR=3.34: p=0.001). Intact immunoglobulin concentration was not prognostic in this study in keeping with current international prognostic guidelines. As with previously published data, FLCr was a prognostic indicator in MM (van Rhee 2007, Kyrtsonis 2007). It is likely FLCr is more predictive of outcome than the concentration of tumour FLC production (data not shown) because it includes a measure of immunoparesis. HLCr was an independent prognostic indicator of survival in this study. HLCr measurement may be superior to intact immunoglobulin in predicting outcomes because: 1) Changes in haematocrit and plasma volume in MM can cause Ig to change by more than 50% regardless of tumour production. 2) Serum IgG is susceptible to variable clearance rates (related to saturation of the FcRn receptor for IgG). 3) Ig measurements using serum protein electrophoresis or nephelometry include all or some of the non-tumour Immunoglobulins and may be non-linear. The summated FLCr and HLCr is a stronger prognostic marker than either measurement independently. This maybe because, as shown by Ayliffe (2007) myeloma cells can produce intact immunoglobulin, FLC or both. Therefore, in patients with very low intact immunoglobulin production and high FLC production, FLCr is likely to be the most prognostic marker and visa versa for patients with low FLC production. Conclusion In this combined study FLCr, HLCr and FLCr + HLCr were found to be predictive of overall survival in MM patients. Larger studies comparing HLCr and FLCr with B2M and Albumin as used in the international staging system are needed. Disclosures Harding: The Binding Site Group Ltd: Employment. Bradley:The Binding Site Group Ltd: Employment. Bradwell:The Binding Site Group Ltd: Shareholder.

Intact Immunoglobulin or Fragments Thereof Can Be Detected in Urine in a Proportion of Patients with Multiple Myeloma and Are Associated with Reduced Survival At Presentation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1828-1828
Author(s):  
Heinz Ludwig ◽  
Philip Young ◽  
Dejan Milosavljevic ◽  
Niklas Zojer ◽  
Wolfgang Hübl ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Binding Site ◽  
Light Chain ◽  
Free Light Chain ◽  
Light Chains ◽  
Glomerular Injury ◽  
Female Ratio ◽  
Serum Free ◽  
Serum Free Light Chain

Abstract Abstract 1828 Introduction: Intact immunoglobulin or fragments thereof (intact/fragmented Ig) can be found in the urine due to nephrotic injury or the preferential scavenging of albumin by the renal FcRn receptor leading to immunoglobulin catabolism. Until now the occurrence, frequency and clinical impact of this phenomenon has not been assessed in patients with multiple myeloma (MM). Here we determine the incidence of intact/fragmented Ig in urine and evaluate its prognostic relevance. Patients and Methods: 94 patients with MM, median age 70 years old (range 41–87) with a male / female ratio 28/66, ISS stage I (48), stage II (23), stage III (28), 69 IgG (43 IgGk/26 IgGl) and 25 IgA (15 IgAk/7 IgAl) were enrolled. Serum free light chain concentrations (sFLC) were measured using commercially available immunoassays (Freelite™, The Binding Site, Birmingham, UK) and compared to electrophoresis results (Hydrasys, Sebia, Paris, France). Overall survival was estimated by the product limiting method of Kaplan-Meyer and survival was compared by the log rank test. Results: Overall, sFLC ratios had a greater sensitivity than urine immunofixation (uIFE) for the detection of monoclonal light chains 86/94 vs. 46/94. In 13/46 (28%) uIFE positive patients intact immunoglobulins or significant fragments (intact/fragmented Ig) thereof were detected, 12 IgG, (12/69, 17%) and 1 IgA (1/25, 4%). Three of these patients had normal urine protein concentrations (<250mg/L) and 2/13 patients had glomerular injury identified by increased levels of albumin excretion. There was no difference in creatinine levels between patients with or without intact/fragmented Ig (p=0.673). Analysis of overall survival in patients stratified at presentation according to uIFE results, namely the presence of intact/fragmented Ig, abnormal serum free light chain ratio-, and negative uIFE results revealed significantly shorter overall survival for the intact/fragmented Ig group (median OS: 34.5 vs. 66.0, vs. 80.6 months, respectively, p< 0.048) (figure 1). Discussion: Our findings confirm the superiority of the serum free light chain assay for detection of monoclonal free light chains as compared to urine immunofixation. However, the serum free light chain assay is inadequate for detection of intact/fragmented Ig in urine. The most important finding presented here is the observation that intact and/or fragment immunoglobulin is present in a substantial number of patients with MM. This phenomenon is mainly restricted to IgG isotypes. There are two possible explanations for these findings: first, the presence of glomerular injury, but this phenomenon (increased albumin leakage) was only seen in two patients and hence is unlikely to account for this observation. The second explanation relies upon disruption of the FcRn receptor function in immunoglobulin scavenging. This receptor will preferentially scavenge albumin in the renal setting, but dysfunction may lead to increased immunoglobulin catabolism and the presence of intact and/or fragmented Ig (Sarav, JASN, 20: 1941–1952, 2009). The results may reflect a hitherto unidentified subtle renal dysfunction. In line with this notion overall survival in our patients intact/fragmented Ig was found to be significantly shorter. Conclusion: We observed an unexpected high incidence of intact/fragmented Ig in the urine of our patients with MM. Patients with urinary excretion of intact/fragmented immunoglobulin had significantly shorter survival. These findings should be validated in further studies. Disclosures: Young: Binding Site: Employment. Harding:Binding Site: Employment.

scholarly journals Serum free light chain measurements to reduce 24-h urine monitoring in patients with multiple myeloma with measurable urine monoclonal protein

2018 ◽  
Vol 93 (10) ◽  
pp. 1207-1210 ◽  
Author(s):  
Marcella Tschautscher ◽  
Vincent Rajkumar ◽  
Angela Dispenzieri ◽  
Martha Lacy ◽  
Morie Gertz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Free Light Chain ◽  
Serum Free ◽  
Monoclonal Protein ◽  
Serum Free Light Chain

scholarly journals Multiple myeloma can be accurately diagnosed in acute kidney injury patients using a rapid serum free light chain test

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Jennifer L. J. Heaney ◽  
John P. Campbell ◽  
Punit Yadav ◽  
Ann E. Griffin ◽  
Meena Shemar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Acute Kidney Injury ◽  
Light Chain ◽  
Kidney Injury ◽  
Free Light Chain ◽  
Serum Free ◽  
Serum Free Light Chain

scholarly journals High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis

Blood ◽  
2007 ◽  
Vol 110 (3) ◽  
pp. 827-832 ◽  
Author(s):  
Frits van Rhee ◽  
Vanessa Bolejack ◽  
Klaus Hollmig ◽  
Mauricio Pineda-Roman ◽  
Elias Anaissie ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Prognostic Significance ◽  
Complete Response ◽  
High Serum ◽  
Free Light Chain ◽  
Response To Therapy ◽  
Rapid Reduction ◽  
Serum Free ◽  
Serum Free Light Chain

Abstract Serum-free light chain (SFLC) levels are useful for diagnosing nonsecretory myeloma and monitoring response in light-chain–only disease, especially in the presence of renal failure. As part of a tandem autotransplantation trial for newly diagnosed multiple myeloma, SFLC levels were measured at baseline, within 7 days of starting the first cycle, and before both the second induction cycle and the first transplantation. SFLC baseline levels higher than 75 mg/dL (top tertile) identified 33% of 301 patients with higher near-complete response rate (n-CR) to induction therapy (37% vs 20%, P = .002) yet inferior 24-month overall survival (OS: 76% vs 91%, P < .001) and event-free survival (EFS: 73% vs 90%, P < .001), retaining independent prognostic significance for both EFS (HR = 2.40, P = .008) and OS (HR = 2.43, P = .016). Baseline SFLC higher than 75 mg/dL was associated with light-chain–only secretion (P < .001), creatinine level 176.8 μM (2 mg/dL) or higher (P < .001), beta-2-microglobulin 297.5 nM/L (3.5 mg/L) or higher (P < .001), lactate dehydrogenase 190 U/L or higher (P < .001), and bone marrow plasmacytosis higher than 30% (P = .003). Additional independent adverse implications were conferred by top-tertile SFLC reductions before cycle 2 (OS: HR = 2.97, P = .003; EFS: HR = 2.56, P = .003) and before transplantation (OS: HR = 3.31, P = .001; EFS: HR = 2.65, P = .003). Unlike baseline and follow-up analyses of serum and urine M-proteins, high SFLC levels at baseline—reflecting more aggressive disease—and steeper reductions after therapy identified patients with inferior survival.

Sign in / Sign up

Export Citation Format

Share Document