Shortcoming of serum B-cell maturation antigen measurement by enzyme-linked immunosorbent assay in one laboratory's experience: Unsatisfactory assay reproducibility.

INTRODUCTION: Serum protein electrophoresis and serum free light chain (SFLC) assays are standard methods for monitoring patients with multiple myeloma (MM). However, patients with non-secretory MM often require invasive bone marrow biopsies to monitor treatment response and disease progression. Recently, serum soluble B-cell maturation antigen (sBCMA) has been proposed as an alternative biomarker for monitoring of MM, including non-secretory disease. We aimed to optimize the performance of and validate a serum sBCMA enzyme-linked immunosorbent assay (ELISA) from R&D Systems for research and eventual clinical use.

METHODS AND RESULTS: A total allowable error of 25 % was used, with one-third (8.3 %) budgeted for imprecision, one-third for bias, and one-half (12.5 %) as the allowable deviation from linearity. For imprecision, the repeatability coefficient of variation (CV) was acceptable, but the within-laboratory CV was not. We were limited in our ability to assess accuracy, but recovery of the ELISA standards was acceptable, and the sBCMA concentrations determined in various patient populations compared well to previous publications. The sBCMA concentration also correlated significantly with the M-protein concentration and the involved/uninvolved SFLC ratio. The sBCMA ELISA was verified to be linear within the allowable deviation between 99.04-1179.36 pg/mL. We attempted to confirm stability of serum sBCMA stored at room temperature, 4 °C, and -20 °C for up to 50 weeks, but the assay reproducibility was too poor for this to be assessed adequately.

CONCLUSION: Despite efforts to optimize the performance of the ELISA, the results were not reproducible enough over time to allow us to implement this sBCMA ELISA for clinical use.