IgM k and IgM l Measurements for the Assessment of Patients with Waldenstr € om ' s

Purpose: Accurate quantification of monoclonal IgM immunoglobulins is essential for response assessment in patients with Waldenstr€ om's macroglobulinaemia (WM). The propensity of IgM to form multimers in serum makes sample evaluation by current laboratory methods particularly challenging. Experimental Design: We assessed the precision and linearity of IgMk and IgMl heavy/light chain (HLC, Hevylite) assays, and established reference intervals using 120 normal donor sera. We compared the quantitative performance ofHLCassayswith serum protein electrophoresis (SPE) and total IgM nephelometry for 78 diagnostic samples and follow-up samples from 25 patients with WM. Comparisons were made between the three methods for diagnostic sensitivity and response assessment. Results: IgMk and IgMl HLC assays showed low imprecision and good linearity. There was good agreement between summated HLC (IgMk þ IgMl) and total IgM (measured nephelometrically; R 1⁄4 0.90), but only moderate agreement between involved IgM HLC and SPE densitometry (R 1⁄4 0.49). Analysis of 120 normal donor sera produced the following normal ranges: IgMk: 0.29–1.82 g/L; IgMl: 0.17–0.94 g/L; IgMk/IgMl ratio: 0.96–2.30. Using these ranges, IgM HLC ratios were abnormal in all WM presentation sera tested, including 15 with non-quantifiable SPE. Despite discordance in quantitation, responses assigned with HLC assays showed excellent agreement to those based on international guidelines using SPE or total IgM; although abnormal HLC ratios indicated residual disease in some patients with negative electrophoresis results. Conclusions: Nephelometric assessment of IgMk and IgMl HLC pairs offers a quantitative alternative to traditional laboratory techniques for the measurement of monoclonal IgM and may aid in the management of WM. Clin Cancer Res; 1–7. 2016