Abstract Objectives This study aimed to perform an extended analytical verification of the Immunoglobulin Isotypes (GAM) for the EXENT ® Analyzer (EXENT ® -GAM) assay, a MALDI-TOF mass spectrometry-based method for detecting and quantifying serum M-proteins in patients with plasma cell dyscrasias, and to compare it with conventional serum protein electrophoresis (SPEP), serum immunofixation electrophoresis (sIFE) and serum free light chains (sFLC) assays. Methods Imprecision, linearity, limit of quantification (LOQ), quantification comparison with SPEP, isotyping concordance with sIFE and sFLC, interference from therapeutic monoclonal antibodies (t-mAbs), sample stability, and reagent lot consistency were evaluated. Results EXENT ® -GAM demonstrated acceptable imprecision (CV ≤20 % for low and ≤15 % for high M-protein levels) and wide linear range (∼0.03–30 g/L). The polyclonal immunoglobulin background negatively influenced the assays LOQ. M-proteins with mass-shifted light chains (i.e., glycosylated light chains) are prone to non-linearity and inferior LOQ. M-protein quantification by EXENT ® differed systematically and proportionally from quantification by SPEP, highlighting non-interchangeability. EXENT ® demonstrated 97 % concordance with sIFE for M-protein isotyping and identified numerous additional (low-level) M-proteins. Some proved to be clinically relevant (residual disease in sIFE-negative samples); others lacked correlation with sFLC result or clinical diagnosis. EXENT ® reliably distinguished endogenous M-proteins from t-mAbs, except talquetamab, which interfered with quantification and was partially misclassified. Conclusions EXENT ® -GAM enables sensitive and reproducible quantification and isotyping of M-proteins below the detection limit of SPEP and sIFE. Its ability to resolve analytical challenges posed by SPEP and sIFE represents a significant advancement. Further clinical studies are needed to confirm its potential in residual disease detection.
Droogenbroeck et al. (Tue,) studied this question.