Quantification of Serum IgMκ and IgMλ In Patients with Waldenstrom's Macroglobulinemia (WM) at Diagnosis and During Disease Course; Clinical Correlations

Abstract

Abstract 3004 Resolution of IgM monoclonal proteins (M-proteins) on serum protein electrophoresis (SPE) can make accurate quantification difficult. The same applies to the determination of total IgM by nephelometry which inherently includes monoclonal and polyclonal immunoglobulins. Specific polyclonal antibodies, which recognise epitopes spanning the junction of the heavy and light chains of the individual immunoglobulin isotypes, have been produced and used to develop nephelometric assays (Hevylite™). The purpose of the present study is to evaluate the prognostic value IgMκ/IgMλ ratios (HLCR) at diagnosis and the role of HLCR in disease monitoring. Retrospective sera from 31 WM patients, 4 IgM-MGUS, 2 IgM-like syndrome at diagnosis and for 9 of them during disease course, were included in the study. Analysis of IgMκ and IgMλ was performed on a Siemens Dade-Behring BN™II nephelometer and results were compared with disease parameters such as blood count, beta2-microglobulin (β2M), serum albumin, lactate dehydrogenase (LDH), and lymphoplasmacytic bone marrow infiltration. Abnormal HLCR were reported in 30/31 WM patients. There was a good correlation between summated IgMκ + IgMλ and total IgM (r=0.832 p0.01). These 12 patients presented polyclonal hypogammaglobulinemia (with regard to their IgG and IgA levels). Median IgM HLCR (expressed as IgMκ/IgMλ or IgMλ/IgMκ with the involved Ig as numerator) were 90.88 (range 1.91–1000) in WM v 17.65 (range 1.08–34.57) in IgM-MGUS (p=0.06). Median IgM HLCR was significantly higher in WM patients requiring treatment (n=24) at presentation than in patients not (n=7) requiring treatment (185.7 v 13.45 p=0.023). IgM HLCR correlated with bone marrow infiltration (p=0.029) and time to first treatment (p=0.003). A simple risk stratification model utilising: IgM HLCR>median, β2M>5 and abnormal LDH, identified 3 prognostic groups with respect to survival (p Disclosures: Mirbahai: Binding Site Group Ltd: Employment. Bradwell:Binding Site: Equity Ownership, Patents & Royalties. Harding:Binding Site Group Ltd: Employment.