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
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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (102)
Jia xiang Jin
1Heidelberg Myeloma Center and German-speaking Myeloma Multicenter Group (GMMG), Heidelberg University Hospital, Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg, Germany
Varun R. Ginde
Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany
Stefanie Huhn
1Heidelberg Myeloma Center and German-speaking Myeloma Multicenter Group (GMMG), Heidelberg University Hospital, Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg, Germany
Philipp Reichert
1Heidelberg Myeloma Center and German-speaking Myeloma Multicenter Group (GMMG), Heidelberg University Hospital, Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg, Germany
Uta Bertsch
1Heidelberg Myeloma Center and German-speaking Myeloma Multicenter Group (GMMG), Heidelberg University Hospital, Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg, Germany
Lisa B. Leypoldt
Department of Oncology, Hematology and BMT, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Thorsten Peters-Regehr
13The Binding Site GmbH, part of Thermo Fisher Scientific, Schwetzingen, Germany
Igor W. Blau
Carsten Müller-Tidow
Steffen Luntz
15Coordination Centre for Clinical Trials (KKS) Heidelberg, Heidelberg, Germany
Christian S. Michel
1Department of Hematology and Oncology, Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
Christoph Lutz
Marc S. Raab
Niels Weinhold
Axel Benner
Peter Findeisen
28MVZ Labor Dr. Limbach und Kollegen, Heidelberg, Germany
Hans J. Salwender
20Asklepios Tumorzentrum Hamburg, AK Altona and AK St. Georg, Hamburg, Germany
Elias K. Mai
Miriam Ahlborn
Joachim Behringer
Helga Bernhard
Britta Besemer
Department of Internal Medicine II, University Tübingen, Tübingen, Germany
Jörg Bittenbring
1José Carreras Center for Immuno- and Gene Therapy and Department of Internal Medicine I, Saarland University Medical School, Homburg, Germany
Igor Wolfgang Blau
14Charité University Medicine Berlin, Medical Clinic, Berlin, Germany
Claus Bolling
Amelie Boquoi
6University Hospital Essen, Department for Hematology and Stem Cell Transplantation, Essen, Germany
Daniel Debatin
Gerlinde Egerer
Roland Fenk
4University Hospital Düsseldorf, Department of Hematology, Oncology and Clinical Immunology, Düsseldorf, Germany
Barbara Ferstl
Stefan Fronhoffs
Tobias Gaska
Bruederkrankenhaus Paderborn, Paderborn, Germany
Thomas Geer
24Diakoneo Clinic Schwäbisch-Hall, Department of Internal Medicine III, Schwäbisch-Hall, Germany
Deniz Gezer
18RWTH Aachen University, Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, Aachen, Germany
Hartmut Goldschmidt
Internal Medicine V, Hematology, Oncology and Rheumatology, German-Speaking Myeloma Multicenter Group Study Group, Heidelberg University Hospital and National Center for Tumor Diseases, Heidelberg, Germany
Martin Görner
Ullrich Graeven
Mathias Hänel
7Department III of Internal Medicine, Klinikum Chemnitz, Chemnitz, Germany
Bernhard Heilmeier
12Hospital Barmherzige Brueder Regensburg, Clinic for Oncology and Hematology, Regensburg, Germany
Michael Heinsch
Gerhard Held
18Klinik für Innere Medizin 1, Westpfalzklinikum, Kaiserslautern, Germany
Martin Hoffmann
Tobias A.W. Holderried
16University Hospital Bonn, Department of Hematology, Oncology, Stem Cell Transplantation, Immune and Cell Therapy, Clinical Immunology and Rheumatology, Bonn, Germany
Olaf Hopfer
Snjezana Janjetovic
20Department of Hematology and Cell Therapy, Helios Klinikum Berlin-Buch, Berlin, Germany
Maika Klaiber-Hakimi
19Marien Hospital Düsseldorf, Clinic for Hematology, Oncology and Palliative Care, Düsseldorf, Germany
Martine Klausmann
Stefan Klein
Wolfgang Knauf
28Centrum für Hämatologie und Onkologie Bethanien, Frankfurt am Main, Germany
Yon-Dschun Ko
Doris Maria Kraemer
Stephan Kremers
Martin Kropff
Paul La Rosée
2Schwarzwald-Baar-Klinikum
Rolf Mahlberg
From Bielefeld University, Medical School and University Medical Center Ostwestfalen-Lippe, Campus Hospital Lippe, Detmold, Germany (J.H.); the Department of Radiation Oncology, Medical University of Graz, Graz, Austria (T.B.); the Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany (C.S.); the Institute of Surgical Pathology, University Medical Center Freiburg, Germany (P.B.); the Department of Surgery, University Medical Center Schleswig-Holstein–Campus Lübeck, Lübeck, Germany (B.K., T.K.); Comprehensive Cancer Center Augsburg, Faculty of Medicine, University of Augsburg, Augsburg, Germany (R.C.); the Department of General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany (S.U.); the Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg–Eppendorf, Hamburg, Germany (J.R.I.); the Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute Universi...
Christoph Mann
10University Hospital Gießen and Marburg, Department for Hematology, Oncology and Immunology, Marburg, Germany
Uwe Martens
19Department of Hematology and Oncology, SLK-Clinics Heilbronn GmbH, Heilbronn, Germany
Ivana von Metzler
Christian Michel
23University Hospital Mainz, Department of Internal Medicine III, Mainz, Germany
Martin Müller
Wolfram Pönisch
Peter Reimer
22Evang. Kliniken Essen-Mitte, Clinic for Hematology, Oncology and Stem Cell Transplantation, Essen, Germany
Claudia Riechel
Armin Riecke
German Military Hospital Ulm, Germany
Hendrik Riesenberg
25Hematology/Oncology Center, Bielefeld, Germany
Mark Ringhoffer
Mathias Rummel
6University Hospital Gießen, Department of Hematology & Oncology, Gießen, Germany
Volker Runde
Hans Jürgen Salwender
Markus Schaich
21Department of Hematology, Oncology and Palliative Care, Rems-Murr-Kliniken, Winnenden, Germany
Christof Scheid
12Hospital Barmherzige Brueder Regensburg, Clinic for Oncology and Hematology, Regensburg, Germany
Martin Schmidt-Hieber
27Department of Hematology and Oncology, Medical University Lausitz–Carl Thiem, Cottbus, Germany
Daniel Schöndube
Roland Schroers
18Medical Clinic II-Hematology and Oncology, Ruhr-University Bochum, Bochum, Germany
Hans-Joachim Schütte
Evgenii Shumilov
1University Hospital Muenster, Department of Medicine A, Hematology, Oncology and Pneumology, Muenster, Germany
Peter Staib
4Department of Haematology and Oncology, St. Antonius Krankenhaus Eschweiler, Eschweiler, Germany
Dirk Strumberg
Hans-Joachim Tischler
11Department of Hematology and Oncology, University Hospital of Minden, Minden, Germany
Karolin Trautmann-Grill
3Department of Medicine I, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany
Walter Verbeek
Rudolf Weide
Eckhart Weidmann
Katja C. Weisel
Maike de Wit
Christiane Bernhardt
Thomas Fietz
Jochen Grassinger
Peter Immenschuh
Georg Köchling
Michael Koenigsmann
Michael Neise
Holger Nückel
Maria Procaccianti
Stefan Schmitt
Fraunhofer Institute for Microtechnology and Microsystems, Mainz, Germany
Andreas Schwarzer
Heike Steiniger
Barbara Tschechne
Michael Varvenne
Bettina Whitlock
Matthias Zaiss
3Practice for interdisciplinary oncology and hematology, Freiburg, Germany
Carsten Ziske