P11 | Peripheral Measurable Residual Disease Activity Assessment by Maldi-tof Mass Spectrometry in Patients With Newly-diagnosed Multiple Myeloma in the Phase 3 Gmmg-hd7 Trial
Year: 2026
Type: article
Abstract: Background. Depth of response is a central determinant of clinical outcomes in multiple myeloma (MM), and bone-marrow-based minimal residual disease (MRD) has emerged as one of the strongest surrogate biomarkers for progression-free (PFS) and overall survival (OS). However, MRD assessment remains invasive, potentially spatially biased, resource-intensive and logistically challenging, restricting its practicability for frequent longitudinal disease monitoring and large-scale implementation in routine practice. Mass spectrometry (MS)-based detection of monoclonal proteins in peripheral blood represents an emerging, promising and minimally invasive alternative. Matrix-assisted laser-desorption/ionization time-of-flight (MALDI-TOF) MS, a top-down light-chain-based method, enables highly sensitive identification and tracking of patient-specific M-proteins, discrimination from therapeutic antibodies, and accurate quantification below the detection limits of conventional serum protein electrophoresis (SPEP) and immunofixation (IFE). While earlier studies (e.g., Puig et al. 2024; Kubicki et al. 2024; Mai et al. 2023; Claveau et al. 2022) already suggested a clinically significant prognostic role for MS-based measurable residual activity (MRA), large prospective evaluations within randomized phase 3 trials are currently limited. The present study addresses this critical gap by evaluating MS-based MRA longitudinally in a large, well-characterized cohort of patients treated within the phase 3 GMMG-HD7 trial.Methods. Serum MS was performed on 3,301 samples from 617 patients enrolled in the phase 3 GMMG-HD7 trial at baseline, post-induction (IND), post-autologous stem cell transplant (ASCT), 12 and 24 months of maintenance (12M MT, 24M MT), end-of-study (EOS), and at progressive disease (PD). MS-based MRA was assessed using the EXENT® system. Bone-marrow MRD was evaluated via Next-Generation Flow cytometry (sensitivity 10-5). Prognostic impact on progression-free survival (PFS) was analyzed at predefined timepoints, alone and in combination with MRD. Multivariate Cox models were fitted considering age, sex, first randomization treatment arm and risk scoring (R-ISS), separately for every landmark.Results. As seen in Figure 1, MS reliably distinguished therapeutic antibodies from patient M-proteins and accurately tracked longitudinal M-protein dynamics. MS negativity strongly predicted superior PFS, most prominently during maintenance (12M MT: HR 0.25; 95% CI 0.15–0.43; adjusted p<0.001). Combined MS/MRD assessment further refined risk stratification: double-positive patients had the poorest outcomes, whereas all other groups exhibited comparably favorable PFS. Concordance between MS and MRD increased over time (post-IND: 62.7%; 12M MT: ~85%), with early discordance influenced by IgG recycling. MS detected low-level residual M-protein with higher sensitivity than serum protein electrophoresis (SPEP), enabling quantification in samples at sub-gram ranges below conventional assay limits. MS/MRD/SPEP/IFE concordant samples were most frequent with all-negative profiles predicting the best outcomes.Conclusions. Serum MS is a sensitive, reproducible, and practical biomarker for detecting and tracking residual disease in MM. It complements MRD, improves risk stratification, and allows minimally invasive monitoring. Integration of MS-based MRA into future response criteria and risk-adapted treatment strategies may define deeper remission states and guide therapy decisions in MM.
Source: Haematologica
Authors: J.X. Jin, V.R. Ginde, S. Huhn, Ph. Reichert, U. Bertsch, R. Fenk, B. Besemer, A. Boquoi, R. Schroers, I. Von Metzler, M. Hänel, Ch. Mann, L.B. Leypoldt, B. Heilmeier, C. Scheid, T. Peters-Regehr, I.W. Blau, C. Müller-Tidow, S. Luntz, T.A.W. Holderried, K. Trautmann-Grill, D. Gezer, M. Klaiber-Hakimi, M. Müller, E. Shumilov, W. Knauf, C.S. Michel, T. Geer, H. Riesenberg, Ch. Lutz, M.S. Raab, N. Weinhold, M. Hoffmann, A. Benner, P. Findeisen, K.C. Weisel, H.J. Salwender, H. Goldschmidt, E.K. Mai
Institutions: Heidelberg University, University Hospital Heidelberg, German Cancer Research Center, National Center for Tumor Diseases, Düsseldorf University Hospital, Universitätsklinikum Tübingen, University of Tübingen, Essen University Hospital, Stiftung Universitätsmedizin Essen, Universitätsklinikum Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Goethe University Frankfurt, University Hospital Frankfurt, Klinikum Chemnitz, Universitätsklinikum Gießen und Marburg, University Medical Center Hamburg-Eppendorf, Krankenhaus Barmherzige Brüder, University Hospital Cologne, Thermo Fisher Scientific (Germany), Charité - Universitätsmedizin Berlin, University Hospital Bonn, University Hospital Carl Gustav Carus, RWTH Aachen University, Marien Hospital Düsseldorf, Klinikum Region Hannover, University of Münster, University Hospital Münster, University Medical Center of the Johannes Gutenberg University Mainz, Klinikum Ludwigshafen, Asklepios
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,157
OpenAlex ID: W7154512895
FWCI:
Cites:
Cited by:
Related to: