Peripheral Measurable Residual Disease Activity Assessment by MALDI-TOF Mass Spectrometry in Patients With Newly Diagnosed Multiple Myeloma in the Phase III GMMG-HD7 Trial

Mass spectrometry (MS) offers a minimally invasive approach for detecting monoclonal proteins in multiple myeloma (MM), but large prospective evaluations remain limited. We analyzed 3,301 serum samples from 617 patients enrolled in the phase III GMMG-HD7 trial to characterize the analytical performance and clinical relevance of MS-based measurable residual activity. MS reliably distinguished therapeutic antibodies, tracked diagnostic M proteins longitudinally, and demonstrated strong prognostic value across defined time points. MS negativity was associated with superior progression-free survival (PFS), with the greatest separation at later time points (12 months of maintenance: hazard ratio, 0.25 [95% CI, 0.15 to 0.43]; adjusted P < .001). Combined assessment with bone-marrow measurable residual disease (MRD) further refined risk stratification: MS/MRD double-positive patients exhibited the worst PFS, whereas all other groups showed comparably favorable outcomes. MS/MRD concordance increased over time and was influenced by immunoglobulin isotype, with expected immunoglobulin G-recycling–associated early discordance. MS provided accurate M-protein detection and outperformed serum protein electrophoresis at low concentrations, reliably quantifying low-level residual disease. These findings establish serum MS as a sensitive, reproducible, and practical biomarker that complements MRD and supports minimally invasive disease monitoring in MM, with potential integration into future response assessment and risk-adapted treatment strategies.

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Publication Details

Journal
Journal of Clinical Oncology
Published
2026-05-21
DOI
https://doi.org/10.1200/jco-25-02957
Primary Topic
Multiple Myeloma Research and Treatments
Type
article
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article

Peripheral Measurable Residual Disease Activity Assessment by MALDI-TOF Mass Spectrometry in Patients With Newly Diagnosed Multiple Myeloma in the Phase III GMMG-HD7 Trial

Amelie Boquoi, Doris Kraemer, Christoph Mann, Philipp Reichert et al.
Journal of Clinical Oncology
Multiple Myeloma Research and Treatments
article

Peripheral Measurable Residual Disease Activity Assessment by MALDI-TOF Mass Spectrometry in Patients With Newly Diagnosed Multiple Myeloma in the Phase III GMMG-HD7 Trial

Amelie Boquoi, Doris Kraemer, Christoph Mann, Philipp Reichert, Mark Ringhoffer, Dirk Strumberg, Snjezana Janjetovic, Christof Scheid, H Goldschmidt, Martin Müller, Armin Riecke, Bernhard Heilmeier, Stefanie Huhn, Wolfgang Knauf, Peter Staib, Axel Benner, S P Luntz, Barbara Ferstl, Thorsten Peters-Regehr, Wolfram Pönisch, Miriam Ahlborn, Roland Schroers, Daniel Schöndube, Rolf Mahlberg, Michael Heinsch, Martin Hoffmann, Peter Findeisen, Daniel Debatin, Stefan Fronhoffs, Claus Bolling, Niels Weinhold, Britta Besemer, Igor Wolfgang Blau, Jia Xiang Jin, Hans Salwender, H. J. Schütte, Ullrich Graeven, Paul La Rosée, Joachim Behringer, Hendrik Riesenberg, K Weisel, Gerlinde Egerer, Stephan Kremers, Thomas Geer, Martine Klausmann, Evgenii Shumilov, Claudia Riechel, Christoph Lutz, Helga Bernhard, Gerhard Held, Volker Runde, Igor W. Blau, Tobias Gaska, Hans‐Joachim Tischler, T Holderried, Stefan Klein, Markus Schaich, M Hänel, R Fenk, Martin Görner, Mathias Rummel, Uta Bertsch, Yon-Dschun Ko, Martin Schmidt-Hieber, Carsten Müller-Tidow, Varun R. Ginde, Peter Reimer, Uwe Martens, Karolin Trautmann-Grill, Deniz Gezer, Lisa B. Leypoldt, Christian S. Michel, Olaf Hopfer, Maika Klaiber-Hakimi, Ivana von Metzler, Jörg Bittenbring, Marc S. Raab, Elias K. Mai, Martin Kropff, Hans J. Salwender
article en

Abstract

Mass spectrometry (MS) offers a minimally invasive approach for detecting monoclonal proteins in multiple myeloma (MM), but large prospective evaluations remain limited. We analyzed 3,301 serum samples from 617 patients enrolled in the phase III GMMG-HD7 trial to characterize the analytical performance and clinical relevance of MS-based measurable residual activity. MS reliably distinguished therapeutic antibodies, tracked diagnostic M proteins longitudinally, and demonstrated strong prognostic value across defined time points. MS negativity was associated with superior progression-free survival (PFS), with the greatest separation at later time points (12 months of maintenance: hazard ratio, 0.25 [95% CI, 0.15 to 0.43]; adjusted P < .001). Combined assessment with bone-marrow measurable residual disease (MRD) further refined risk stratification: MS/MRD double-positive patients exhibited the worst PFS, whereas all other groups showed comparably favorable outcomes. MS/MRD concordance increased over time and was influenced by immunoglobulin isotype, with expected immunoglobulin G-recycling–associated early discordance. MS provided accurate M-protein detection and outperformed serum protein electrophoresis at low concentrations, reliably quantifying low-level residual disease. These findings establish serum MS as a sensitive, reproducible, and practical biomarker that complements MRD and supports minimally invasive disease monitoring in MM, with potential integration into future response assessment and risk-adapted treatment strategies.

Journal of Clinical Oncology
Goethe University Frankfurt (DE), Universität Hamburg (DE), German Cancer Research Center (DE), Johannes Gutenberg University Mainz (DE), Medical University of Graz (AT), Heidelberg University (DE), Universitätsklinikum Gießen und Marburg (DE), University Hospital Bonn (DE), University Hospital Heidelberg (DE), Asklepios Klinik Altona (DE), Cardiovascular Center Bethanien (DE), Düsseldorf University Hospital (DE), University Hospital Münster (DE), Klinikum Region Hannover (DE), University Medical Center Hamburg-Eppendorf (DE), National Center for Tumor Diseases (DE), Universitätsklinikum Knappschaftskrankenhaus Bochum (DE), Medizinisches Versorgungszentrum Prof. Mathey, Prof. Schofer (DE), Essen University Hospital (DE), Krankenhaus Barmherzige Brüder (DE), University Children's Hospital Tübingen (DE), Klinikum Ludwigshafen (DE), Klinikum Bielefeld (DE), Marien Hospital Düsseldorf (DE), University Hospital Frankfurt (DE), University Hospital Cologne (DE), Thermo Fisher Scientific (Germany) (DE), Klinikum Chemnitz (DE), Heinrich Heine University Düsseldorf (DE), Technische Universität Dresden (DE), Charité - Universitätsmedizin Berlin (DE), RWTH Aachen University (DE)
Good health and well-being
Openalex Percentile: Top 6%
Multiple Myeloma Research and Treatments
DOISourceOpenAlex
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