Evaluation of ims-IP assay for the detection and typing of monoclonal immunoglobulins by mass spectrometry.

Abstract

Abstract Background: Serum and urine protein electrophoresis have long served as the mainstay for monitoring monoclonal protein (M-protein) levels in assessing treatment response for multiple myeloma (MM). Despite limitations in sensitivity and specificity, these methods remain the primary clinical detection techniques.Intact Mass Spectrometry-Immunoprecipitation Assay（iMS-IP Assay) is the new methods for detecting M-proteins that have emerged in the past two years. Methods: Leftover serum samples previously analyzed by immunofixation electrophoresis (IFE) were tested using the iMS-IP assay. We evaluated the accuracy, sensitivity, and specificity of the iMS-IP assay and preliminarily assessed its potential utility for minimal residual disease (MRD) monitoring in peripheral blood and distinguishing therapeutic monoclonal antibodies (t-mAbs) within a clinical cohort. Results: The iMS-IP assay demonstrated high concordance with IFE for M-protein detection while exhibiting superior sensitivity. Agreement between iMS-IPAssay & IFE was of 97.8% for IgG κ (87/89), 95.9% for IgG λ (47/49), 97.9% for IgA κ (46/47), 100% for IgA λ (46/46), 92.1% for IgM κ (35/38), 50% for IgM λ (4/8) , 73.7% for Free κ (14/19), 88.2% for Free λ (30/33). Discordances intact immunoglobulin was due to samples with two M-Ig, where IFE wasn't able to identify the major clone.The analytical sensitivity was 0.1g/L for the M-protein typing of IgG, 0.05g/L for IgA and 0.01g/L for IgM. The sensitivity is 10-fold higher than that of IFE.For MRD detection, the iMS-IP assay identified M-proteins with identical m/z to baseline samples in all 3 patients with clinically confirmed complete response (CR). Furthermore, in one serum sample from a newly diagnosed patient previously classified as non-secretory by IFE, the iMS-IP assay detected a Free κ M-protein. For the distinction of t-mAbs, the mass spectrometry-based method correctly identified t-mAbs in 87.5% (7/8) of cases, significantly outperforming IFE. Conclusions: This is the first study in China to confirm the consistency and sensitivity of the results between iMS-IP assasy detection and immunofixation electrophoresis detection.The iMS-IP assay shows potential to replace IFE and advance M-protein screening, diagnosis, and monitoring. Further validation of its clinical sensitivity and specificity is warranted to explore its feasibility for peripheral blood MRD assessment. Disclosure : None declared