Combined use of free light chain and heavy/light chain ratios allow diagnosis and monitoring of patients with monoclonal gammopathies: Experience of a single institute, with three exemplar case reports

Abstract

Monoclonal gammopathies are characterized by serum monoclonal component (MC) plus an intact immunoglobulin and a free light chain (FLC), or a combination of both. The measurement of FLC with Freelite® is the standard practice recommended by International Myeloma Working Group guidelines. Recently, Hevylite® heavy/light chains (HLC) assays were introduced to specifically target junctional epitopes between the heavy and light chains of intact immunoglobulins, allowing the independent quantification of the involved (MC) and uninvolved (polyclonal immunoglobulin background) HLC isotype. Between January 2012 and March 2014, 90 patients were examined: 49 multiple myeloma (MM), 6 smoldering MM (SMM) and 35 monoclonal gammopathy of undetermined significance (MGUS). Of these 90 patients, 300 samples were collected at different times. The diagnostic and monitoring contribution of Hevylite A and G assays was assessed in all 90 patients examined. Additionally, 3 representative cases were selected. The Hevylite absolute values and ratio demonstrated high sensitivity and specificity with respect to serum protein electrophoresis and serum immunofixation. The combined use of Hevylite A and G with Freelite was particularly useful in dubious cases with more than one MC or with co-migrating components, as well as in the course of monitoring to assess the independent change of FLC and HLC, possibly reflecting the presence of clonal heterogeneity in the cohort. From this study, it can be concluded that FLC and HLC are independent, useful markers to monitor the MC and to assess with greater specificity and sensitivity the effect of therapy, thereby providing clinical support. Further studies are required to assess the prognostic potential of Hevylite in MGUS and SMM.

The Current Role of the Heavy/Light Chain Assay in the Diagnosis, Prognosis and Monitoring of Multiple Myeloma: An Evidence-Based Approach

“…However, this MM patient relapsed only secreting monoclonal intact Igs, without showing abnormal serum FLC ratio [26]. This observation suggests that it could be interesting to monitor both HLC and FLC parameters to follow the evolution of clones secreting different types of MPs, as suggested by Gagliardi and colleagues [40]. Additionally, Chae et al observed an alteration of the HLCr in two patients in CR due to decreased uHLC levels.…”

Laboratory and Clinical Settings of Heavy/Light Chain (HLC) Assays in the Management of Monoclonal Gammopathies and Multiple Myeloma

“…Ludwig et al demonstrate that rHLC was the first proof of relapse in MM patients relapsing only intact immunoglobulins without any abnormal serum FLC ratios (FLCr) [35]. This evidence encourages the monitoring of both FLC and HLC criteria, analyzing the evolution of clones secreting diverse types of MCs [35,49].…”

Serum Hevylite® assay in the differential diagnosis of patients with high suspicion of AL Amyloidosis

“…The HLC assays provide an alternative tool to aid in the management of diseases associated with monoclonal intact Ig, including monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and intact Ig MM 13 . Previous studies found that HLC assays have an important prognostic role and may well assist in monitoring patients, both for benign and AL PCDs 12,14 . In relation to patients with MGUS, a study found that HLC assays provided information about the risk of malignant transformation 15‐17 .…”