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Utility of serum free light chain measurements in multiple myeloma patients not achieving complete response to therapy.

ABSTRACT: Normalization of the serum-free light-chain ratio (FLCr) with the absence of bone marrow monoclonal plasma cells following achievement of a complete response (CR) to therapy denotes a stringent CR in multiple myeloma (MM), and is associated with improved overall survival (OS). However, its value in patients achieving

SUBMITTER: Alhaj Moustafa M

PROVIDER: S-EPMC4598254 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Utility of serum free light chain measurements in multiple myeloma patients not achieving complete response to therapy.

Alhaj Moustafa M M Rajkumar S V SV Dispenzieri A A Gertz M A MA Lacy M Q MQ Buadi F K FK Hwa Y L YL Dingli D D Kapoor P P Hayman S R SR Lust J A JA Kyle R A RA Kumar S K SK

Leukemia 20150512 10

Normalization of the serum-free light-chain ratio (FLCr) with the absence of bone marrow monoclonal plasma cells following achievement of a complete response (CR) to therapy denotes a stringent CR in multiple myeloma (MM), and is associated with improved overall survival (OS). However, its value in patients achieving <CR is not clear. We hypothesized that patients achieving a normalization of FLCr with initial therapy of MM will have an improved outcome, even in the absence of a CR. We retrospec ...[more]

PMID: 25962523

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Prognostic utility of serum free light chain ratios and heavy-light chain ratios in multiple myeloma in three PETHEMA/GEM phase III clinical trials.

Project description:We investigated the prognostic impact and clinical utility of serum free light chains (sFLC) and serum heavy-light chains (sHLC) in patients with multiple myeloma treated according to the GEM2005MENOS65, GEM2005MAS65, and GEM2010MAS65 PETHEMA/GEM phase III clinical trials. Serum samples collected at diagnosis were retrospectively analyzed for sFLC (n = 623) and sHLC (n = 183). After induction or autologous transplantation, 309 and 89 samples respectively were available for sFLC and sHLC assays. At diagnosis, a highly abnormal (HA) sFLC ratio (sFLCr) (<0.03 or >32) was not associated with higher risk of progression. After therapy, persistence of involved-sFLC levels >100 mg/L implied worse survival (overall survival [OS], P = 0.03; progression-free survival [PFS], P = 0.007). Among patients that achieved a complete response, sFLCr normalization did not necessarily indicate a higher quality response. We conducted sHLC investigations for IgG and IgA MM. Absolute sHLC values were correlated with monoclonal protein levels measured with serum protein electrophoresis. At diagnosis, HA-sHLCrs (<0.29 or >73) showed a higher risk of progression (P = 0.006). Additionally, involved-sHLC levels >5 g/L after treatment were associated with shorter survival (OS, P = 0.001; PFS, P = 0.018). The HA-sHLCr could have prognostic value at diagnosis; absolute values of involved-sFLC >100 mg/L and involved-sHLC >5 g/L could have prognostic value after treatment.

| S-EPMC6128544 | biostudies-literature

Serum free light chains, not urine specimens, should be used to evaluate response in light-chain multiple myeloma.

Project description:Guidelines for monitoring multiple myeloma (MM) patients expressing light chains only (light-chain MM [LCMM]) rely on measurements of monoclonal protein in urine. Alternatively, serum free light chain (sFLC) measurements have better sensitivity over urine methods, however, demonstration that improved sensitivity provides any clinical benefit is lacking. Here, we compared performance of serum and urine measurements in 113 (72κ, 41λ) newly diagnosed LCMM patients enrolled in the Intergroupe Francophone du Myélome (IFM) 2009 trial. All diagnostic samples (100%) had an abnormal κ:λ sFLC ratio, and involved (monoclonal) FLC (iFLC) expressed at levels deemed measurable for monitoring (≥100 mg/L). By contrast, only 64% patients had measurable levels of monoclonal protein (≥200 mg per 24 hours) in urine protein electrophoresis (UPEP). After 1 and 3 treatment cycles, iFLC remained elevated in 71% and 46% of patients, respectively, whereas UPEP reported a positive result in 37% and 18%; all of the patients with positive UPEP at cycle 3 also had elevated iFLC levels. Importantly, elevated iFLC or an abnormal κ:λ sFLC ratio after 3 treatment cycles associated with poorer progression-free survival (P = .006 and P < .0001, respectively), whereas positive UPEP or urine immunofixation electrophoresis (uIFE) did not. In addition, patients with an abnormal κ:λ sFLC ratio had poorer overall survival (P = .022). Finally, early normalization of κ:λ sFLC ratio but not negative uIFE predicted achieving negative minimal residual disease, as determined by flow cytometry, after consolidation therapy (100% positive predictive value). We conclude that improved sensitivity and prognostic value of serum over urine measurements provide a strong basis for recommending the former for monitoring LCMM patients.

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Comparison of serum free light chain and urine electrophoresis for the detection of the light chain component of monoclonal immunoglobulins in light chain and intact immunoglobulin multiple myeloma.

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

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| S-EPMC6949235 | biostudies-literature

Serum N-Glycans: A New Diagnostic Biomarker for Light Chain Multiple Myeloma.

Project description:The aim of this study was to evaluate the diagnostic and differential diagnostic power of serum N-glycans for light chain multiple myeloma (LCMM). A total of 167 cases of subjects, including 42 LCMM, 42 IgG myeloma, 41 IgA myeloma, and 42 healthy controls were recruited in this study. DNA sequencer-assisted fluorophore-assisted capillary electrophoresis (DSA-FACE) was applied to determine the quantitive abundance of serum N-glycans. The core fucosylated, bisecting and sialylated modifications were analyzed in serum of LCMM patients (n=20) and healthy controls (n=20) randomly selected from the same cohort by lectin blot. Moreover, serum sialic acid (SA) level was measured by enzymatic method. We found two N-glycan structures (NG1A2F, Peak3; NA2FB, Peak7) showed the optimum diagnostic efficacy with area under the ROC curve (AUC) 0.939 and 0.940 between LCMM and healthy control. The sensitivity and specificity of Peak3 were 88.1% and 92.9%, while Peak7 were 92.9% and 97.6%, respectively. The abundance of Peak3 could differentiate LCMM from IgG myeloma with AUC 0.899, sensitivity 100% and specificity 76.2%, and Peak7 could be used to differentiate LCMM from IgA myeloma with AUC 0.922, sensitivity 92.9% and specificity 82.9%. Serum SA level was significantly higher in patients with LCMM than that in healthy controls. Moreover, the decreased core fucosylation, bisecting and increased sialylation characters of serum glycoproteins were observed in patients with LCMM. We concluded that serum N-glycan could provide a simple, reliable and non-invasive biomarker for LCMM diagnosis and abnormal glycosylation might imply a new potential therapeutic target in LCMM.

| S-EPMC4468189 | biostudies-literature

Prognostic Impact of Serum Free Light Chain Ratio Normalization in Patients with Multiple Myeloma Treated within the GMMG-MM5 Trial.

Project description:We investigated the prognostic impact of time-dependent serum free light chain ratio (FLCr) normalization in 590 patients with secretory multiple myeloma (MM) during first-line treatment within the German-Speaking Myeloma Multicenter Group MM5 trial. Serum free light chains (sFLC) were assessed by the Freelite test at baseline, after induction, mobilization, autologous blood stem cell transplantation, consolidation and every three months during maintenance or follow up within two years after the start of maintenance. The proportion of patients with a normal or normalized FLCr increased from 3.6% at baseline to 23.2% after induction and 64.7% after consolidation. The achievement of FLCr normalization at any one time before the start of maintenance was associated with significantly prolonged progression-free survival (PFS) (p < 0.01, hazard ratio (HR) = 0.61, 95% confidence interval (95% CI) = 0.47-0.79) and overall survival (OS) (p = 0.02, HR = 0.67, 95% CI = 0.48-0.93) in multivariable time-dependent Cox regression analyses. Furthermore, reaching immune reconstitution, defined as the normalization of uninvolved immunoglobulins, before maintenance was associated with superior PFS (p = 0.04, HR = 0.77, 95% CI = 0.60-0.99) and OS (p = 0.01, HR = 0.59, 95% CI = 0.41-0.86). We conclude that FLCr normalization during therapy is an important favorable prognostic factor in MM. Therefore, we recommend serial measurements of sFLC during therapy until achieving FLCr normalization, even in patients with secretory MM.

| S-EPMC8507729 | biostudies-literature

Light chain myeloma and detection of free light chains in serum and urine of dogs and cats.

Project description:BackgroundDetection of free light chains (fLC) in animals relies on protein electrophoresis or the Bence-Jones protein test on urine.ObjectiveTo describe the detection of both serum fLC (sfLC) and urine fLC (ufLC) in 8 dogs and 2 cats using a commercially available human immunofixation (IF) kit.AnimalsArchived serum or urine samples from 27 dogs and 2 cats submitted to the Colorado State University Veterinary Diagnostic Laboratory for routine diagnostics.MethodsRetrospective study evaluating the presence of fLC in dogs and cats using agarose gel electrophoresis and routine and fLC IF performed on serum and urine. The performance of the fLC IF reagents was evaluated using samples characterized by routine IF, tandem mass spectrometry, and a combination of fLC IF and western blotting. Free light chains were documented by paired electrophoresis and fLC IF.ResultsThe fLC only myeloma case developed end-stage renal failure 5 months post initial diagnosis. All electrophoresis-defined urinary Bence-Jones proteins were labeled by the anti-free λ light chain (anti-fλ) reagent; none were labeled by the anti-free κ light chain (anti-fκ); 2 of these were identified as fκ by mass spectrometry. An electrophoretically identical protein restriction that was labeled by the anti-fλ reagent was present in the paired serum from 5/8 of cases, documenting sfLC.Conclusions and clinical importanceCommercially available human IF reagents identified sfLC and ufLC in both dogs and cats. Free light chains may be nephrotoxic in dogs.

| S-EPMC7995444 | biostudies-literature

Incidence and clinical characteristics of multiple myeloma with low M-protein levels and normal values of hemoglobin, creatinine, calcium, and serum free light chain ratio.

Project description: Not available

| S-EPMC8027460 | biostudies-literature

Dysphagia unveiling systemic immunoglobulin light-chain amyloidosis with multiple myeloma.

Project description:Dysphagia is an uncommon presentation of systemic immunoglobulin light-chain (AL) amyloidosis with multiple myeloma (MM). Gastrointestinal (GI) involvement usually manifests with altered motility, malabsorption or bleeding. Furthermore, patients identified with GI amyloidosis, without previous diagnosis of a plasma cell disorder, are extremely rare. We report an elderly woman who presented with acute on chronic cardiac dysfunction, sick sinus syndrome and acute renal failure. While admitted, she developed intermittent dysphagia to both solids and liquids. Oesophagogastroduodenoscopy showed ulcerations of oesophagus and duodenum. Biopsies revealed focal amyloid deposition, stained with Congo red. Renal biopsy revealed amyloid deposition in renal arterioles. She underwent a bone marrow biopsy confirming MM, represented by more than 15% plasma cell population. She was started on treatment for heart failure, induction chemotherapy for MM and percutaneous gastrostomy tube for feeding. However, she continued to deteriorate, eventually opting for hospice, and ultimately died 2?days after discharge from hospital.

| S-EPMC6202992 | biostudies-literature

Comparison of 2 Serum-Free Light-Chain Assays in CKD Patients.

Project description:IntroductionQuantification of serum-free light chains (FLCs) is important in the diagnosis and monitoring of paraprotein-related diseases. There are currently 2 FLC assays available: the Freelite assay (Binding Site) and the N Latex assay (Siemens). There is emerging evidence that these assays give different results, but it is not established how kidney dysfunction affects these assays differently.MethodsIn this study, we measured and compared serum FLCs in patients with mild-to-moderate chronic kidney disease (CKD) using both assays.ResultsAlthough κ FLCs are higher by Freelite, λ FLCs are higher by N Latex. Both κ and λ FLCs correlate inversely with estimated glomerular filtration rate (eGFR) in the 2 assays, but this effect is more pronounced in λ-free light-chain measurement by N Latex. Consequently, although the κ/λ ratio by Freelite is inversely correlated by eGFR, the κ/λ ratio by N Latex is positively correlated with eGFR.ConclusionOur results clearly demonstrate that the 2 available FLC assays cannot be used interchangeably in patients with CKD.

| S-EPMC7210599 | biostudies-literature

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