Clinical usefulness of free light chain concentration as a tumor marker in multiple myeloma

Abstract

Monoclonal immunoglobulin, as a marker for monoclonal gammopathy, is evaluated by protein electrophoresis (PEP) and immunofixation electrophoresis (IFE). However, PEP and IFE are not satisfactory in sensitivity, objectivity, and facility. Recently, a highly sensitive, automated immunoassay for measurement of free light chain (FLC) concentrations in serum and urine has been developed for the identification and monitoring of patients with monoclonal gammopathy. To explore the clinical usefulness of measurement of FLC concentrations, we measured the kappa and lambda FLC concentrations and calculated the kappa/lambda FLC ratios for three groups [multiple myeloma (MM), other diseases, and control] and compared the results of the FLC assay with the results of PEP or IFE. The concentrations of serum kappa and lambda FLCs and the kappa/lambda FLC ratios for the MM group and non-MM groups were distinct. In the MM group, some sera and urine samples had no evidence of M protein on PEP and IFE, but FLC assay showed abnormal concentrations of FLCs and abnormal kappa/lambda FLC ratios in most cases. As compared with the PEP, the kappa/lambda FLC ratio revealed higher sensitivity in all diagnostic ranges with different cutoff values. Particularly, when the cutoff value 2.0 for kappa/lambda FLC ratio was used, specificity and positive predictive value were largely improved than when the cutoff values 1.2 and 1.5 were used. These findings indicated that FLC assay enables to detect myeloma patients with very low M protein due to early stage or after therapy and to distinguish patients with monoclonal increase of FLC from patients with polyclonal increase of FLC due to other conditions, particularly using kappa/lambda FLC ratio 0.3-2.0 as a diagnostic range. Despite some technical limitations of the assay, the incorporation of kappa/lambda FLC ratios with FLC concentrations is useful in the detection of M protein, particularly with negative serum or urine IFE results, and differentiation of monoclonal gammopathies from patients with polyclonal increase in FLC due to other conditions.

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

“…The present study shows higher sensitivity when a cut-off threshold of 2.0 for the k/l ratio was used, compared to serum PE (96.6% vs. 86.4%) in detecting MM. This finding is in agreement with that of other studies (15,16). The sensitivity was 100% when both assays were used.…”

“…Using a cut-off threshold of 2.0 for the FLC ratio, 100% PPV and 96.8% NPV was noted, enabling us to differentiate polyclonal gammopathy from MM. Similar findings have been reported by Kang et al (15). The present study shows higher sensitivity when a cut-off threshold of 2.0 for the k/l ratio was used, compared to serum PE (96.6% vs. 86.4%) in detecting MM.…”

International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders

“…1 Serum FLC immunoassays have a sensitivity of less than 1 mg/l. 4 The conclusion drawn from these studies and others 11,[23][24][25][26] is that for the purpose of screening for monoclonal proteins for all diagnoses except AL, the FLC can replace the 24 h urine IFE; however, once a diagnosis of monoclonal gammopathy is made, the 24 h protein IFE should be done. For AL screening, however, the urine IFE should still be done in addition to the serum tests including the serum FLC.…”

“…Both patients and physicians are reluctant to do 24-h urine collections because of the inconvenience posed, but depending on the indication for the original monoclonal protein study of the blood, they could be missing at least 10-17% of cases with either AL amyloidosis or LCMM by doing serum IFE alone. 11,14 The ease of performing the FLC measurement could rectify this deficiency and lead to earlier diagnosis of these disorders.…”

Recommendations for Use of Free Light Chain Assay in Monoclonal Gammopathies

“…Serum FLC immunoassays have a sensitivity of less than 1 mg/L (4). The conclusion drawn from these studies and others (12)(13)(14)(15)(16) is that for the purpose of screening for monoclonal proteins for all diagnoses except AL, the FLC can replace the 24 hour urine IFE; yet, once a diagnosis of MG is made, the 24 hour protein IFE should be done. For AL screening, however, the urine IFE should still be done in addition to the serum tests including the serum FLC.…”