Heavy/light chain assay as a biomarker for diagnosis and follow-up of multiple myeloma

Abstract Background The heavy-light chain (HLC) assay enables the accurate measurement of each isotype-specific heavy and light chain (i.e., IgGĸ, IgGλ, IgAĸ, and IgAλ) and the derivation of an HLC-pair ratio. However, to date, only limited data have validated the usefulness of serial HLC measurements in the routine follow-up of intact immunoglobulin multiple myeloma (MM) patients. Methods A total of 36 diagnostic and 671 post-treatment sera from 115 IgG and 61 IgA MM patients were assessed with capillary zone electrophoresis, immunosubtraction electrophoresis, total immunoglobulin measurement, free light chain, and HLC assay. The correlations between M-protein levels and the HLC and FLC assay-derived parameters were examined and the clinical significance of the biomarkers was evaluated according to patients' status. Results Involved HLC (iHLC) was the best biomarker correlating with M-protein concentration in both IgG and IgA MM, and could provide a surrogate marker substituting M-protein levels to follow the course of the disease, especially in β-migrating IgA M-proteins. The distribution of iHLC values as well as HLC-pair ratios (rHLC) yielded significantly different results among the various response categories in both IgG and IgA MM. In addition, we detected 2 cases in which an abnormal rHLC in a stringent complete remission (sCR) sample was a marker of early non-symptomatic relapse. Conclusion In this study of a cohort of 176 patients in a routine clinical setting, we have provided evidence of the clinical utility of real world HLC assays for the identification of M-proteins and to monitor M-proteins with an emphasis on IgA monoclonal gammopathies.