Immunoglobulin heavy/light chain analysis enhances the detection of residual disease and monitoring of multiple myeloma patients

Abstract

AimTo evaluate the clinical utility of incorporating a novel heavy/light chain immunoassay (HLC) into the existing methods for the assessment of multiple myeloma (MM) patients.MethodsConvenience sera samples from 90 previously treated IgG and IgA MM patients in different disease stages were analyzed. The study was conducted in Clinical Hospital Center Zagreb between 2011 and 2013. The collected sera were analyzed by standard laboratory techniques (serum protein electrophoresis, quantification of total immunoglobulins, serum immunofixation, serum free light chain [FLC] assay) and HLC assay.ResultsHLC ratios outside the normal range were found in 58 of 90 patients, including 28 out of 61 patients with total immunoglobulin measurements within the normal range and 5 out of 23 patients in complete response. Both elevated HLC isotype level and abnormal HLC ratio correlated with the parameters of tumor burden, including percentage of plasma cells in the bone marrow (P < 0.001 and P = 0.002, respectively) and an abnormal serum FLC ratio (for both P < 0.001). In addition, abnormal HLC isotype level correlated with serum beta-2-microglobulin level (P = 0.038). In terms of prognosis, abnormal HLC isotype level and abnormal HLC ratio were significantly associated with shorter overall survival (P < 0.001 and P = 0.002, respectively). Interestingly, suppression of the uninvolved (polyclonal) isotype pair, but not other non-myeloma immunoglobulin isotypes, was also associated with a shorter overall survival (P = 0.021). In a multivariate analysis, an abnormal HLC ratio and β2-microglobulin level >3.5mg/L were independent risk factors for survival.ConclusionThe new HLC assay has greater sensitivity in detecting monoclonal protein, correlates with tumor burden markers, and affects patients' outcome.

Heavy+light chain monitoring correlates with clinical outcome in multiple myeloma patients

“…First, we found good agreement between standard IMWG (electrophoretic) and HLC assays for response assignment, with the significant exception of patients at conventional VGPR, where HLC ratios had normalised and BMPC were <5% in approximately 50% of cases, suggesting a deeper level of response (⩾CR) in these patients. Similar differences have been reported elsewhere: Suehara et al 39 and Batinic et al 40 reported 55 and 41%, respectively, of a combined 170 patients at VGPR, had normal HLC ratios, whereas Ludwig et al 24 identified 12/35(34%) IFE-positive patients at VGPR or nCR as having normal HLC ratios. Here for the first time we also show that the substantial proportion of patients at standard VGPR but whose HLC ratios have normalised have a significantly smaller risk of progression.…”

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

“…In addition, IMI was found to be significantly correlated with a shortened PFS in this cohort of patients [56]. Concordant results obtained at the end of consolidation were reported by Michallet et al, both in all patients and only in those in conventional ≥CR [34], and by Batinic and colleagues in their cohort of 90 unselected MM patients at different stages of the disease [37].…”

“…The lower the iHLC/uHLC ratio, the deeper the response reached [26]. Similar results were found by Batinic et al in a subset of 90 unselected MM patients at different stages of the disease, in which 100% of patients in PR, 59% in VGPR and 22% in CR showed an abnormal HLCr [37]. In line with those results, the aforementioned Spanish group reported 100%, 100%, 88%, 66% and 48% of patients with abnormal HLCr in progressive disease (PD), stable disease (SD), PR, VGPR and CR in their study [21].…”

Patients assigned to VGPR, PR, and SD in the IMWG response category are composed of heterogeneous population when assessed by the heavy/light chain assay

“…Similar results have been reported by other investigators as shown in Table where the number and percentages of patients who obtained a VGPR but had normal rHLC are shown: Suehara et al reported a normal rHLC in 69 out of 116 VGPR patients (59.4%) . Batinic et al reported a normal rHLC in 41.2% . And Ludwig et al identified that 12 patients (34.3%) out of 35 IFE positive patients with VGPR or nCR (ie, CR with positive IFE) had a normal rHLC .…”