Monitoring M-Protein, Therapeutic Antibodies, and Polyclonal Antibodies in a Multiparametric Mass Spectrometry Assay Provides Insight into Therapy Response Kinetics in Patients with Multiple Myeloma
<b>Background/Objectives:</b> Multiple Myeloma (MM) is a hematologic malignancy caused by clonally expanded plasma cells that produce a monoclonal immunoglobulin (M-protein), a personalized biomarker. Recently, we developed an ultra-sensitive mass spectrometry method to quantify minimal...
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| author | Charissa Wijnands Peter G. A. Karel Jolein Gloerich Gad Armony Anastasia Tzasta Corrie M. de Kat Angelino Luciano Di Stefano Vincent Bonifay Theo M. Luider Martijn M. VanDuijn Sandra J. Croockewit Elizabeth A. de Kort Daan A. R. Castelijn Claudia A. M. Stege Hans J. C. T. Wessels Alain J. van Gool Niels W. C. J. van de Donk Joannes F. M. Jacobs |
| author_facet | Charissa Wijnands Peter G. A. Karel Jolein Gloerich Gad Armony Anastasia Tzasta Corrie M. de Kat Angelino Luciano Di Stefano Vincent Bonifay Theo M. Luider Martijn M. VanDuijn Sandra J. Croockewit Elizabeth A. de Kort Daan A. R. Castelijn Claudia A. M. Stege Hans J. C. T. Wessels Alain J. van Gool Niels W. C. J. van de Donk Joannes F. M. Jacobs |
| author_sort | Charissa Wijnands |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Multiple Myeloma (MM) is a hematologic malignancy caused by clonally expanded plasma cells that produce a monoclonal immunoglobulin (M-protein), a personalized biomarker. Recently, we developed an ultra-sensitive mass spectrometry method to quantify minimal residual disease (MS-MRD) by targeting unique M-protein peptides. Therapeutic antibodies (t-Abs), key in MM treatment, often lead to deep and long-lasting responses. However, t-Abs can significantly decrease the total polyclonal immunoglobulin (Ig) levels which require supplemental IgG infusion. Here, we demonstrate the simultaneous monitoring of M-proteins, t-Abs, and polyclonal Ig-titers using an untargeted mass spectrometry assay, offering a comprehensive view of therapy response. <b>Methods:</b> Sera collected between 2013 and 2024 from four patients and cerebrospinal fluid (CSF) from one patient who received various t-Abs were analyzed with MS-MRD. M-protein sequences were obtained with a multi-enzyme de novo protein sequencing approach. Unique peptides for M-proteins and t-Abs were selected based on linearity, sensitivity, and slope coefficient in serial dilutions. Ig constant regions were monitored using isotype-specific peptides. <b>Results:</b> The MS-MRD multiplex analysis provided detailed information on drug concentrations and therapy response kinetics. For example, in two patients with refractory disease over five lines of therapy, the MS-MRD analysis showed that the deepest responses were achieved with bispecific t-Ab (teclistamab) treatment. M-protein and t-Ab were also detectable in the CSF of one patient with MS-MRD. <b>Conclusions:</b> This proof-of-concept study shows that the multiplex monitoring of the M-protein, any t-Ab combination, and all Ig-isotypes within one mass spectrometry run is feasible and provides unique insight into therapy response kinetics. |
| format | Article |
| id | doaj-art-cab40b0cc8c5402e8115fcf34fba0341 |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-cab40b0cc8c5402e8115fcf34fba03412025-01-24T13:46:06ZengMDPI AGPharmaceutics1999-49232025-01-0117113510.3390/pharmaceutics17010135Monitoring M-Protein, Therapeutic Antibodies, and Polyclonal Antibodies in a Multiparametric Mass Spectrometry Assay Provides Insight into Therapy Response Kinetics in Patients with Multiple MyelomaCharissa Wijnands0Peter G. A. Karel1Jolein Gloerich2Gad Armony3Anastasia Tzasta4Corrie M. de Kat Angelino5Luciano Di Stefano6Vincent Bonifay7Theo M. Luider8Martijn M. VanDuijn9Sandra J. Croockewit10Elizabeth A. de Kort11Daan A. R. Castelijn12Claudia A. M. Stege13Hans J. C. T. Wessels14Alain J. van Gool15Niels W. C. J. van de Donk16Joannes F. M. Jacobs17Laboratory Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsLaboratory of Clinical Chemistry, Deventer Ziekenhuis, 7416 SE Deventer, The NetherlandsTranslational Metabolic Laboratory, Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsTranslational Metabolic Laboratory, Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsLaboratory Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsLaboratory Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsSebia, 91090 Lisses, FranceSebia, 91090 Lisses, FranceDepartment of Neurology, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Neurology, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Hematology, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsDepartment of Hematology, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsDepartment of Hematology, Amsterdam University Medical Centers, 1081 HV Amsterdam, The NetherlandsDepartment of Hematology, Erasmus Medical Center, 3015 GD Rotterdam, The NetherlandsTranslational Metabolic Laboratory, Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsTranslational Metabolic Laboratory, Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsDepartment of Hematology, Amsterdam University Medical Centers, 1081 HV Amsterdam, The NetherlandsLaboratory Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands<b>Background/Objectives:</b> Multiple Myeloma (MM) is a hematologic malignancy caused by clonally expanded plasma cells that produce a monoclonal immunoglobulin (M-protein), a personalized biomarker. Recently, we developed an ultra-sensitive mass spectrometry method to quantify minimal residual disease (MS-MRD) by targeting unique M-protein peptides. Therapeutic antibodies (t-Abs), key in MM treatment, often lead to deep and long-lasting responses. However, t-Abs can significantly decrease the total polyclonal immunoglobulin (Ig) levels which require supplemental IgG infusion. Here, we demonstrate the simultaneous monitoring of M-proteins, t-Abs, and polyclonal Ig-titers using an untargeted mass spectrometry assay, offering a comprehensive view of therapy response. <b>Methods:</b> Sera collected between 2013 and 2024 from four patients and cerebrospinal fluid (CSF) from one patient who received various t-Abs were analyzed with MS-MRD. M-protein sequences were obtained with a multi-enzyme de novo protein sequencing approach. Unique peptides for M-proteins and t-Abs were selected based on linearity, sensitivity, and slope coefficient in serial dilutions. Ig constant regions were monitored using isotype-specific peptides. <b>Results:</b> The MS-MRD multiplex analysis provided detailed information on drug concentrations and therapy response kinetics. For example, in two patients with refractory disease over five lines of therapy, the MS-MRD analysis showed that the deepest responses were achieved with bispecific t-Ab (teclistamab) treatment. M-protein and t-Ab were also detectable in the CSF of one patient with MS-MRD. <b>Conclusions:</b> This proof-of-concept study shows that the multiplex monitoring of the M-protein, any t-Ab combination, and all Ig-isotypes within one mass spectrometry run is feasible and provides unique insight into therapy response kinetics.https://www.mdpi.com/1999-4923/17/1/135multiple myelomatherapeutic drug monitoringminimal residual diseasetherapy response kineticstherapeutic antibodybispecific antibody |
| spellingShingle | Charissa Wijnands Peter G. A. Karel Jolein Gloerich Gad Armony Anastasia Tzasta Corrie M. de Kat Angelino Luciano Di Stefano Vincent Bonifay Theo M. Luider Martijn M. VanDuijn Sandra J. Croockewit Elizabeth A. de Kort Daan A. R. Castelijn Claudia A. M. Stege Hans J. C. T. Wessels Alain J. van Gool Niels W. C. J. van de Donk Joannes F. M. Jacobs Monitoring M-Protein, Therapeutic Antibodies, and Polyclonal Antibodies in a Multiparametric Mass Spectrometry Assay Provides Insight into Therapy Response Kinetics in Patients with Multiple Myeloma Pharmaceutics multiple myeloma therapeutic drug monitoring minimal residual disease therapy response kinetics therapeutic antibody bispecific antibody |
| title | Monitoring M-Protein, Therapeutic Antibodies, and Polyclonal Antibodies in a Multiparametric Mass Spectrometry Assay Provides Insight into Therapy Response Kinetics in Patients with Multiple Myeloma |
| title_full | Monitoring M-Protein, Therapeutic Antibodies, and Polyclonal Antibodies in a Multiparametric Mass Spectrometry Assay Provides Insight into Therapy Response Kinetics in Patients with Multiple Myeloma |
| title_fullStr | Monitoring M-Protein, Therapeutic Antibodies, and Polyclonal Antibodies in a Multiparametric Mass Spectrometry Assay Provides Insight into Therapy Response Kinetics in Patients with Multiple Myeloma |
| title_full_unstemmed | Monitoring M-Protein, Therapeutic Antibodies, and Polyclonal Antibodies in a Multiparametric Mass Spectrometry Assay Provides Insight into Therapy Response Kinetics in Patients with Multiple Myeloma |
| title_short | Monitoring M-Protein, Therapeutic Antibodies, and Polyclonal Antibodies in a Multiparametric Mass Spectrometry Assay Provides Insight into Therapy Response Kinetics in Patients with Multiple Myeloma |
| title_sort | monitoring m protein therapeutic antibodies and polyclonal antibodies in a multiparametric mass spectrometry assay provides insight into therapy response kinetics in patients with multiple myeloma |
| topic | multiple myeloma therapeutic drug monitoring minimal residual disease therapy response kinetics therapeutic antibody bispecific antibody |
| url | https://www.mdpi.com/1999-4923/17/1/135 |
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