Bridging the gap between therapeutic progress and diagnostic precision
According to the International Myeloma Foundation, more than 176,000 people are diagnosed with multiple myeloma worldwide each year. Advances in therapy have transformed outcomes, yet accurate diagnosis remains challenging. Current diagnostic pathways often depend on techniques that are difficult to interpret and may not detect low-level disease.
Most multiple myeloma cases are characterized by the presence of a monoclonal protein in the blood that is produced by a malignant plasma cell clone in the bone marrow.
Traditional electrophoretic methods such as serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) have long been used to assess monoclonal proteins. However, these assays may lack the analytical sensitivity required to detect very low concentrations of monoclonal proteins and can be influenced by therapeutic monoclonal antibodies leading to potential uncertainty in clinical decision making.
To address these limitations, Binding Site developed the EXENT® System, which combines automated immunoprecipitation with MALDI-ToF mass spectrometry (MS) for sensitive, specific, as well as objective identification and measurement of a patient’s serum monoclonal protein. The EXENT System is a non-invasive method certified for clinical use, offering diagnostic clarity and confidence.
The EXENT System: A modern approach to monoclonal protein detection
The EXENT System provides a fully integrated approach to monoclonal protein assessment, from sample preparation to results reporting. Designed to ease daily clinical practice it delivers high analytical sensitivity and minimises subjectivity in results interpretation.
Main benefits include:
- Specific identification and calculated measurement of a patient’s monoclonal protein
- Detection and flagging of known therapeutic monoclonal antibodies
- Enhanced clinical sensitivity led by identification of low-concentration monoclonal proteins
- Detection of post-translational modifications
Mass spectrometry: delivering clinical clarity
Mass spectrometry is a long-established analytical technique now gaining ground in hematology for its ability to provide detailed molecular information. Its clinical application in monoclonal gammopathies has been recognised by the International Myeloma Working Group (IMWG), whose Mass Spectrometry Committee endorsed the method as a replacement for IFE in both clinical trials and practice.¹
Each patient’s monoclonal immunoglobulin exhibits a unique molecular "fingerprint," measurable as a precise mass-to-charge ratio. In healthy individuals, MALDI-ToF spectra show a smooth, polyclonal distribution of κ and λ light chains. In contrast, patients with a monoclonal gammopathy exhibit a sharp, discrete peak rising above this polyclonal background – a clear signal of monoclonal protein production.
This objective and sensitive readout allows users to precisely identify a disease-related monoclonal protein that is patient specific and can detect and flag monoclonal proteins from known therapeutic antibodies thereby improving accuracy at diagnosis.
In addition, when combined with Optilite® IgG, IgA, and IgM assays, the EXENT System provides information on monoclonal protein concentration in patient serum samples.
With standardized and informative results, the EXENT System provides greater clarity and diagnostic confidence, ultimately supporting improved patient care.
A new dimension in disease insights: Detecting mass-shifted light chains
Beyond improving detection sensitivity, MALDI-ToF MS enables new insights into the biological characteristics of monoclonal proteins. Using the EXENT GAM Assay*, clinicians can now identify mass-shifted light chains (MSLs) – indicative of glycosylated immunoglobulin light chains. These appear as broadened or irregular clusters in the spectrum, reflecting post-translational modification of the protein.
This capability has meaningful clinical implications. In a recent case study New perspectives in monoclonal proteins, the EXENT GAM Assay identified and quantified glycosylated light chains that conventional methods would likely overlook.
Supporting evidence from Dispenzieri et al. (2020) showed that glycosylated monoclonal light chains are associated with an increased risk of disease progression:²
The ability to identify glycosylated light chains represents a new dimension in disease assessment—one that may allow earlier recognition of patients at higher risk of progression and guide closer monitoring or intervention strategies.
Conclusion
The diagnostic landscape in plasma cell disorders is evolving rapidly, leading to the need of more precise and sensitive tools. The EXENT System represents a major advancement in monoclonal protein testing – uniting the sensitivity of mass spectrometry with the reliability of automation and the clarity of objective interpretation.
By providing unparalleled sensitivity in serum, more accurate assessment, and greater insights into disease biology, the EXENT System strengthens diagnostic confidence for every patient with monoclonal gammopathy.
*EXENT GAM Assay refers to Immunoglobulin Isotypes (GAM) for the EXENT® Analyser
The EXENT® System combines EXENT® Analyser with the Immunoglobulin Isotypes (GAM) for the EXENT® Analyser.
EXENT and Optilite are registered trademarks of The Binding Site Group Limited (Birmingham, UK) in certain countries. Product availability is subject to country specific regulatory requirements.
References
- Murray DL, et al. Blood Cancer J. 2021; 11:24.
- Dispenzieri A, et al. Leukemia. 2020; 34:2749–2753.