Pre transplant achievement of very good partial response results in improved survival in myeloma

Abstract

Introduction: Serum protein electrophoresis (SPE) and total immunoglobulin measurements are recommended to quantify monoclonal immunoglobulins (M-Ig) for monitoring multiple myeloma (MM) patients. However SPE measurements may be inaccurate at low M-Ig concentrations or when the M-Ig comigrates with other serum proteins. Total IgA (tIgA), although accurate, cannot distinguish between monoclonal and polyclonal immunoglobulin components. Novel heavy/light chain immunoassays (HLC) may provide an alternative method to accurately quantify M-Ig. Here we assess the performance of these assays for monitoring MM patients. Materials and methods: Presentation and follow-up sera from 61 IgA MM patients (37 IgA , 24 IgA ) were measured for HLC IgA and IgA using Hevylite immunoassays (The Binding Site Group Ltd, Birmingham, UK). Results were compared to published HLC reference ranges (IgA (g/L): 0.48-2.82, IgA (g/L): 0.36-1.98, IgA /IgA : 0.80-2.04), historic SPE, immunofixation and tIgA concentrations. Quantitative results were compared using Pearson’s correlation. Responses were assigned following IMWG criteria. Concordance between methods for response assessment was investigated using Weighted Kappa (WK) analysis. Results: Presentation sera from all 61 patients had both abnormal HLC ratios (HLCr) and elevated involved HLC (iHLC) concentrations (median (range); IgA patients: HLCr1⁄4233 (10-6226), iHLC1⁄434 (6-79) g/L; IgA patients: HLCr1⁄40.0119 (0.0003-0.1181), iHLC1⁄429 (6-72.0) g/L). M-IgA concentrations were measurable by SPE in only 40/61 (66%) patients; in the remaining 21/61 (33%) patients nephelometric tIgA measurements were used as surrogate for paraprotein levels. In presentation and follow-up samples there was good correlation for M-Ig levels between iHLC and SPE (y 1⁄4 0.88x+0.88, R2 1⁄4 0.87) as well as between iHLC and tIgA (y 1⁄4 0.87x-0.68, R2 1⁄4 0.90) measurements. iHLC percentage change during follow-up also showed good agreement with changes in SPE (y 1⁄4 1.31x+0.25, R2 1⁄4 0.87) and tIgA (y 1⁄4 0.94x-0.03, R2 1⁄4 0.90). Weighted Kappa analysis demonstrated near-perfect agreement between the responses assigned by either changes in iHLC (89% agreement, WK(95% CI)1⁄40.92 (0.84-1.00)) or HLCr (73% agreement, WK(95% CI)1⁄40.86 (0.81-0.91)) and SPE/tIgA. Conclusion: HLC immunoassays show good agreement with standard methods for quantifying M-IgA and for