Comprehensive Clinical Evaluation of the Exent Analyzer for Detection and Characterization of Monoclonal Gammopathies
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Accurate detection and characterization of serum monoclonal proteins are essential for the diagnosis and management of monoclonal gammopathies. The Immunoglobulin Isotypes (GAM) assay on the EXENTTM Analyzer (The Binding Site, part of Thermo Fisher Scientific) [henceforth described as the EXENT GAM assay] uses mass spectrometry to detect, isotype, and quantify intact monoclonal immunoglobulins in a single workflow. We evaluated the clinical performance of the EXENT analyser across a broad spectrum of monoclonal gammopathies. Methods Residual serum samples were analyzed at three independent centers. The study included patients with clinically confirmed IgG, IgA, or IgM monoclonal gammopathies, disease controls, healthy subjects, and a cross-reactivity cohort. Patients with light chain-only and IgD monoclonal gammopathies were excluded. EXENT analyzer results were compared with clinical diagnosis and with conventional serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE). A positive EXENT analyzer result was defined as detection of an intact IgG, IgA, or IgM M-protein at or above the FDA-cleared isotype-specific diagnostic cut-offs (IgG ≥0.359 g/L, IgA ≥0.325 g/L, and IgM ≥0.197 g/L). Results below these thresholds were classified as negative. Diagnostic sensitivity and specificity were determined, while agreement with conventional testing was assessed for M-protein detection, isotype assignment, and quantification. Results Among 688 patients with monoclonal gammopathies, the EXENT GAM assay demonstrated an overall diagnostic sensitivity of 94.3% (95% CI, 92.3–95.8), including 92.1% for MGUS, 98.6% for smouldering MM, 94.4% for MM, 98.4% for Waldenström macroglobulinemia, and 89.6% for AL amyloidosis. Diagnostic specificity was 87.8% (95% CI, 85.1–90.1) in 655 disease controls. Overall positivity was comparable to SPE (94.3% vs 93.5%) and higher in AL amyloidosis (89.6% vs 80.5%). EXENT showed 95.3% concordance with IFE for isotype assignment and good quantitative agreement with SPE for IgG and IgA monoclonal proteins. As expected, IgM quantification showed a positive bias relative to SPE because of methodological differences between total immunoglobulin measurement and densitometry. Conclusion The EXENT GAM assay demonstrated high clinical sensitivity for detecting intact IgG, IgA, and IgM monoclonal gammopathies across multiple disease settings while providing accurate isotype characterization and quantitative assessment.
Authors: Jill PAULI, Nick PACIARONI, Syreeta ALLEN, Gemma MALIN, Cristina SIMION, Alex BREAN, Habib EL-KHOURY, Julia COLCHIE, Luca BERTAMINI, Erica M HOROWITZ, Irene GHOBRIAL, Grace FLEMING, Zianya M SOLIS, Kaleb Benjamin MCLENDON, John J ROBACK, Andrew S NEISH, Sarah K GREWAL, Ashutosh WECHALEKAR, David M FOUCAUD, Manisha BUTHANI, Nohemi CABALLERO, Maria Florencia DELGADO, Elyara Maria SOARES, Oscar BERLANGA, Stephen HARDING
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223103340