The evolving use of serum free light chain assays in haematology

Pratt, Guy

doi:10.1111/j.1365-2141.2008.07079.x

Cited by 81 publications

(66 citation statements)

References 71 publications

(69 reference statements)

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“…The prognostic role of unbalanced light chain production has been described at urinary level (7) and, more recently, serum level (10,20). Our data confirm that a finding of excess light chains is a risk factor.…”

Section: Discussionsupporting

confidence: 85%

Proposal and Validation of Prognostic Scoring Systems for IgG and IgA Monoclonal Gammopathies of Undetermined Significance

Rossi

Petrucci

Guffanti

et al. 2009

Clinical Cancer Research

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Purpose:The presenting clinico-hematologic features of 1,283 patients with IgG and IgA monoclonal gammopathies of undetermined significance (MGUS) were correlated with the frequency of evolution into multiple myeloma (MM). Experimental Design: Two IgG MGUS populations were evaluated: a training sample (553 patients) and a test sample (378 patients); the IgA MGUS population consisted of 352 patients. Results: Forty-seven of the 553 training group patients and 22 of 378 test group IgG patients developed MM after a median follow-up of 6.7 and 3.6 years, respectively. Multivariate analysis showed that serum monoclonal component (MC) levels of V1.5 g/dL, the absence of light-chain proteinuria and normal serum polyclonal immunoglobulin levels defined a prognostically favorable subset of patients, and could be used to stratify the patients into three groups at different 10-year risk of evolution (hazard ratio, 1.0, 5.04, 11.2; P < 0.001). This scoring system was validated in the test sample. Thirty of the 352 IgA patients developed MM after a median follow-up of 4.8 years, and multivariate analysis showed that hemoglobin levels of <12.5 g/dL and reduced serum polyclonal immunoglobulin correlated with progression. A pooled statistical analysis of all of the patients confirmed the validity of Mayo Clinic risk model showing that IgA class, serum MC levels, and light-chain proteinuria are the most important variables correlated with disease progression. Conclusions: Using simple variables, we validated a prognostic model for IgG MGUS. Among the IgA cases, the possible prognostic role of hemoglobin emerged in addition to a decrease in normal immunoglobulin levels.Monoclonal gammopathies of undetermined significance (MGUS) are the most common forms of plasma cell dyscrasia, with a prevalence of 3% in the general adult population ages >50 years. The incidence of MGUS increases with age, and is >5% in patients ages >70 years (1). By definition, serum monoclonal component (MC) concentrations are V3 g/dL and bone marrow plasma cell counts <10%; there is no related organ or tissue impairment and no evidence of multiple myeloma (MM), macroglobulinemia, amyloidosis, or other related plasma cell or lymphoproliferative disorders (2). As MGUS have a rate of malignant evolution of f1% per year (3 -6), it is important to identify the features at diagnosis that are capable of predicting neoplastic transformation. In a previous study of a limited series of IgG MGUS patients, we found that serum MC levels, the presence or absence of light-chain proteinuria, normal or decreased polyclonal immunoglobulin levels, and the percentage of bone marrow plasma cells were the most reliable variables in predicting different clinical outcomes (7). On the basis of these data, we also identified a subset of IgG MGUS patients at low risk of evolution for whom we proposed a noninvasive diagnostic approach, without bone marrow Imaging, Diagnosis, Prognosis

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Section: Discussionsupporting

confidence: 85%

Proposal and Validation of Prognostic Scoring Systems for IgG and IgA Monoclonal Gammopathies of Undetermined Significance

Rossi

Petrucci

Guffanti

et al. 2009

Clinical Cancer Research

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“…In two patients, the serum FLC ratio was within the reference interval, although serum PE showed the presence of M-protein. It has been reported that in 10% of IIMM, the k/l ratio can be normal (11,12). However, in our study, serum PE was not helpful in diagnosing MM in eight patients (10%), and the M-protein was detected either by IFE or urine PE.…”

Section: Discussioncontrasting

confidence: 41%

Serum free light chains: diagnostic and prognostic value in multiple myeloma

Sthaneshwar

Nadarajan²,

A.S.Maniam³

et al. 2009

Clinical Chemistry and Laboratory Medicine

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Background: Measurement of serum free light chains (FLCs) has recently become available for the diagnosis and monitoring of patients with plasma cell dyscrasias. The aim of this study was to investigate the performance of the serum FLC assay as a tumour marker by comparing FLC concentrations with serum protein electrophoresis (PE) results in the diagnosis of multiple myeloma (MM). In addition, we also evaluated the prognostic value of the baseline serum FLC ratio in patients with MM. Methods: We measured FLC concentrations and calculated the kappa/lambda (k/l) FLC ratios for three groups (control, polyclonal gammopathy and MM). Results:The FLC ratio at a cut-off threshold of 2.0 showed higher sensitivity and specificity compared with serum electrophoresis for the diagnosis of MM. We used the median FLC ratio of )57.5 and -0.04 for k and l secretors, respectively, for assessing survival. Survival was 30 months in patients with the k/l ratio of )57.5 and -0.04 compared to 47 months in patients with the ratio -57.5 and )0.04, indicating that more abnormal serum FLC ratios are associated with poorer survival (p-0.011). Conclusions: Despite the limitations of the assay, the results of our study indicate that the FLC assay in combination with serum PE has an increased sensitivity in the diagnosis of MM. Also, baseline measurement of the k/l ratio provides prognostic information in these same patients.

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“…1 Serum assays offer many advantages over the traditional, electrophoretic, urine FLC assays [2][3][4] and have been used widely as an aid for the diagnosis and management of myeloma patients. The International Myeloma Working Group (IMWG) guidelines currently recommend the use of serum FLC (sFLC) assays in diagnostic screening panels and as a "biomarker of malignancy" (involved-to-uninvolved sFLC ratio $100) defining the presence of multiple myeloma (MM) in the absence of other indications.…”

Section: Introductionmentioning

confidence: 99%

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

Dejoie

Corre

Caillon

et al. 2016

Blood

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International audienceGuidelines 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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The evolving use of serum free light chain assays in haematology

Cited by 81 publications

References 71 publications

Proposal and Validation of Prognostic Scoring Systems for IgG and IgA Monoclonal Gammopathies of Undetermined Significance

Proposal and Validation of Prognostic Scoring Systems for IgG and IgA Monoclonal Gammopathies of Undetermined Significance

Serum free light chains: diagnostic and prognostic value in multiple myeloma

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

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