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Anti-CD3/CD7 immunoconjugate (T-Guard) for severe, steroid-refractory GVHD: final report of BMT CTN 2002

Bone Marrow Transplantation volume 58, pages 1416–1418 (2023)Cite this article

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Allogeneic hematopoietic cell transplant (alloHCT) cures many malignant and non-malignant hematological disorders, but graft vs. host disease (GVHD) remains a common cause of transplant-related morbidity and mortality. Acute GVHD tissue injury is often a consequence of damage associated with conditioning and further driven by donor T lymphocyte antigen recognition and cell activation. Systemic corticosteroids are the first-line treatment for acute GVHD, yet an estimated 10–50% of patients will fail to respond to corticosteroids, with a markedly shortened overall survival [1,2,3,4,5].

Ruxolitinib, a dual JAK1/2 inhibitor, is approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of steroid refractory acute GVHD (SR-aGVHD), and while the overall response rate (ORR) at day 28 with this agent is around 60%, complete response (CR) rates are low (34%) [6], especially for those with grade III-IV SR-aGVHD, (25%) [6, 7]. Optimizing treatment for patients with severe SR-aGVHD is a high priority to improve transplant outcomes.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Support for this study was provided by grants U10HL069294 and U24HL138660 to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung, and Blood Institute and the National Cancer Institute along with contributions by Xenikos BV. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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Author notes

  1. These authors contributed equally: John E. Levine, Gérard Socié.

Authors and Affiliations

  1. Center for Hematologic Malignancies, Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA

    Gabrielle Meyers & Richard T. Maziarz

  2. BMT & Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin and Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    Mehdi Hamadani

  3. Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, and Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA

    Michael Martens

  4. Division of Leukemia, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical, Duarte, CA, USA

    Haris Ali

  5. Centre Hospitalier Universitaire de Nantes, Nantes, France

    Patrice Chevallier

  6. Division of Hematology, The Ohio State University Comprehensive Cancer Center – The James, Columbus, OH, USA

    Hannah Choe

  7. MSK Kids Stem Cell Transplantation and Cellular Therapies, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Andrew C. Harris

  8. Universitätsklinikum Regensburg, Regensburg, Germany

    Ernst Holler

  9. Xenikos BV, Nijmegen, The Netherlands

    Eric van Hooren, Willem Klaassen & Ypke van Oosterhout

  10. National Heart, Lung, and Blood Institute, Bethesda, MD, USA

    Eric Leifer

  11. H. Lee Moffitt Cancer Center, Tampa, FL, USA

    Lia Perez

  12. Division of Oncology, BMT and Leukemia Section, Washington University School of Medicine, St. Louis, MO, USA

    Iskra Pusic

  13. Universitätsklinikum Münster (UKM), Münster, Germany

    Matthias Stelljes

  14. Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands

    Walter van der Velden

  15. Universitair Medisch Centrum Groningen, Groningen, The Netherlands

    Emanuele Ammatuna

  16. Hematology Department, CHU Lille, Lille, France

    David Beauvais

  17. Institut de Cancérologie Lucien Neuwirth, Saint-Priest-en-Jarez, France

    Jérôme Cornillon

  18. Universitaetsklinikum Carl Gustav Carus Dresden, Dresden, Germany

    Johannes Schetelig

  19. The Emmes Company, Rockville, MD, USA

    Jennifer Romeril

  20. Blood and Marrow Transplantation & Cellular Therapy Program, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    Margaret L. MacMillan

  21. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    John E. Levine

  22. Hematology Transplantation, Hospital St Louis and University Paris Cité, Paris, France

    Gérard Socié

Authors
  1. Gabrielle Meyers
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  2. Mehdi Hamadani
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  3. Michael Martens
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  4. Haris Ali
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  5. Patrice Chevallier
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  6. Hannah Choe
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  7. Andrew C. Harris
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  8. Ernst Holler
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  9. Eric van Hooren
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  10. Willem Klaassen
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  11. Eric Leifer
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  12. Ypke van Oosterhout
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  13. Lia Perez
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  14. Iskra Pusic
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  15. Matthias Stelljes
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  16. Walter van der Velden
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  17. Emanuele Ammatuna
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  18. David Beauvais
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  19. Jérôme Cornillon
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  20. Richard T. Maziarz
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  21. Johannes Schetelig
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  22. Jennifer Romeril
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  23. Margaret L. MacMillan
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  24. John E. Levine
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  25. Gérard Socié
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Contributions

GM was a member of the protocol team (Study Chairperson) and responsible for the designing and writing of the protocol, oversight of the study, screening for participants to this trial, interpreting data results, writing the report, including references and table. MH was a member of the protocol team (Protocol Officer), responsible for designing and writing the protocol, responsible for oversight of the protocol, interpreting data results, review and editing of the report. MM was a member of the protocol team, was responsible for the design of and writing the statistical components of the protocol, interpreting data results, review and editing of the report. HA was a member of the protocol team, responsible for the designing and writing of the protocol, was involved in screening and enrollment of participants to this trial, reviewed and edited the report. PC was responsible for the screening and enrollment of participants to this trial and the review and editing of the report. HC was a member of the protocol team, responsible for the designing and writing of the protocol, responsible for screening participants to this trial and reviewed and edited the report. ACH was a member of the protocol team, responsible for the designing and writing of the protocol, and reviewed and edited the report. EH was a member of the protocol team, responsible for designing and writing the protocol, and reviewed and edited the report. EvH was a member of the protocol team, responsible for the designing and writing of the protocol, oversight of the study, interpreting data results and reviewed and edited the report. WK was a member of the protocol team, responsible for the designing and writing of the protocol, oversight of the study, interpreting data results and reviewed and edited the report. EL was a member of the protocol team, responsible for the designing and writing of the protocol, in particular the statistical components of the protocol, interpreting data results, review and editing of the report. YvO was a member of the protocol team, responsible for the design of the protocol, oversight of the study, interpreting data results and reviewed and edited the report. LP was a member of the protocol team, responsible for the designing and writing of the protocol, and reviewed and edited the report. IP was a member of the protocol team, responsible for the designing and writing the protocol, responsible for screening participants to this trial and reviewed and edited the report. MS was a member of the protocol team, responsible for the designing and writing of the protocol, responsible for the screening and enrollment of participants to this trial and reviewed and edited the report. WvdV was a member of the protocol team, responsible for the designing and writing of the protocol, and reviewed and edited the report. EA was responsible for the screening and enrollment of participants to this trial and the review and editing of the report. DB was responsible for the screening and enrollment of participants to this trial and the review and editing of the report. JC was responsible for the screening and enrollment of participants to this trial and the review and editing of the report. RTM was responsible for the screening and enrollment of participants to this trial and the review and editing of the report. JS was responsible for the screening and enrollment of participants to this trial and the review and editing of the report. JR was a member of the protocol team, responsible for the designing and writing of the protocol, was involved in data acquisition and analysis. MLM was involved in protocol creation and the review and editing of the report. JEL was a member of the protocol team (Study Chairperson) and responsible for the designing and writing of the protocol, oversight of the study, screening and enrollment of participants to this trial, interpreting data results, writing and editing the report. GS was a member of the protocol team (Study Chairperson) and responsible for the designing and writing of the protocol, oversight of the study, screening for participants to this trial, interpreting data results, writing and editing the report.

Corresponding author

Correspondence to Gabrielle Meyers.

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Competing interests

EvH, WK and YvO are employees of Xenikos and own equity in Xenikos. MH: Consultancy: Incyte Corporation, MorphoSys, SeaGen, Gamida Cell, Novartis, Legend Biotech, Kadmon, ADC Therapeutics; Omeros, CRISPR, Genmab, Kite, BMS, Caribou, Abbvie. Speaker’s Bureau: Sanofi Genzyme, AstraZeneca, BeiGene, ADC Therapeutics, Kite. Data Monitoring Committee: Myeloid Therapeutics, Inc, Genentech. HC: Research funding: Opna, Scientific Advisory Board: Incyte. EH: Scientific Advisory Board: Novartis, Medac, Pharmabiome and Maat Pharma. RTM Consultancy: Novartis, Artiva, Incyte, Kite, BMS. Research funding: Novartis, Allovir, and Orca. Data Safety Monitoring Board Service: Novartis, Century Therapeutics, VOR Pharma and Athersys. ACH: Consultancy: Janssen and Incyte. GS: Scientific Advisory Board: Novartis, Incyte, AlloVIR, Sanofi. JEL: Research funding: Genentech, Incyte, and Mesoblast, Consultancy: Bluebird Bio, Editas, Equillium, Incyte, Inhibrx, Kamada, Mesoblast, Sanofi, and X4 Pharmaceuticals, Royalties: Viracor (GVHD biomarker patent). DB: Consultancy: BMS, Gilead.

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Meyers, G., Hamadani, M., Martens, M. et al. Anti-CD3/CD7 immunoconjugate (T-Guard) for severe, steroid-refractory GVHD: final report of BMT CTN 2002. Bone Marrow Transplant 58, 1416–1418 (2023). https://doi.org/10.1038/s41409-023-02110-4

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  • DOI: https://doi.org/10.1038/s41409-023-02110-4

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