Positive results from recent clinical trials have significantly expanded current therapeutic options for patients with chronic graft-versus-host disease (GVHD). However, new insights into the associations between clinical characteristics of chronic GVHD, pathophysiologic mechanisms of disease, and the clinical and biological effects of novel therapeutic agents are required to allow for a more individualized approach to treatment. The current report is focused on setting research priorities and direction in the treatment of chronic GVHD. Detailed correlative scientific studies should be conducted in the context of clinical trials to evaluate associations between clinical outcomes and the biological effect of systemic therapeutics. For patients who require systemic therapy but not urgent initiation of glucocorticoids, clinical trials for initial systemic treatment of chronic GVHD should investigate novel agents as monotherapy without concurrently starting glucocorticoids, to avoid confounding biological, pathological, and clinical assessments. Clinical trials for treatment-refractory disease should specifically target patients with incomplete or suboptimal responses to most recent therapy who are early in their disease course. Close collaboration between academic medical centers, medical societies, and industry is needed to support an individualized, biology-based strategic approach to chronic GVHD therapy.
Bibliographical noteFunding Information:
Special acknowledgement goes to the Meredith Cowden GVHD Foundation, France Lymphome Espoir, NBMTLink, Anthony Nolan, the National Marrow Donor Program, BMT InfoNet, and other patient advocacy groups for partnering and collaboration. Thanks to all working groups and consensus conference participants, professional societies, US government agencies, and stakeholders in the field of HSCT for the generous donation of their work, time, talents, and expertise. Particular acknowledgment to the ASTCT and EBMT for their roles in the dissemination, education, and implementation of the concepts and best practices evolving from this project. Special thanks to the independent external peer reviewers who provided their comments and critiques to the 2020 National Institutes of Health (NIH) Chronic GVHD Consensus Project: Nicolaus Kröger, MD, Professor and Clinical Director, Department of Stem Cell Transplantation, University of Hamburg, Hamburg, Germany and President, EBMT; Ryotaro Nakamura, MD, Professor and Director of the Center for Stem Cell Transplantation, City of Hope Cancer Center, Duarte, California; John DiPersio, MD, PhD Chief, Division of Oncology, Director, Center for Gene and Cellular Immunotherapy, Deputy Director, Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri; Mark Juckett, MD, Professor and Director, Blood and Marrow Transplant Program, University of Wisconsin, Madison, Wisconsin; George Chen, MD, Associate Professor of Medicine, University at Buffalo, Buffalo, New York; Rafael Duarte, MD, PhD, FRCP, Head, Department of Hematology and Director, Hematopoietic Transplant Program, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain; Franco Locatelli, MD, Professor of Pediatrics, Università Sapienza, Head, Department of Pediatric Hematology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy; Areej El-Jawahri, MD, Associate Professor, Director, Bone Marrow Transplant Survivorship Program, and Associate Director, Cancer Outcomes Research and Education Program, Massachusetts General Hospital, Boston, Massachusetts; Robert Soiffer, MD, Professor, Chief, Division of Hematologic Malignancies, Chair, Executive Committee for Clinical Programs, Vice Chair, Department of Medical Oncology, Chief, Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts; Daniel Weisdorf, MD, Professor of Medicine and Deputy Director, Clinical Science and Translational Science Institute; Director, Clinical and Translational Research Services, University of Minnesota, Minneapolis, Minnesota; Keith Sullivan. MD, Professor of Medicine, Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, North Carolina; Catherine Lee, MD, Assistant Professor, Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah; Jose Antonio Perez-Simon, MD, Professor of Hematology, University of Seville, Head, Department of Hematology, University Hospital Virgen del Rocio and Vice Director, Biomedical Research Institute of Seville (IBIS), Seville, Spain; Doris Ponce, MD, Associate Professor of Medicine, Hematologic Oncologist, Memorial Sloan Kettering Cancer Center, New York, New York; and Andrew Harris, MD, Assistant Professor of Pediatrics, Pediatric BMT and Cellular Therapy Program, University of Utah/Primary Children's Hospital, Salt Lake City, Utah. Financial disclosure: Funding and implementation of this Consensus Project is made possible through support by the Intramural Program of the National Cancer Institute (NCI) Center for Cancer Research and the NIH Intramural and Extramural Research Programs Institutes and Centers. The opinions expressed are those of the authors and do not represent the position of the NCI, the NIH, or the US Government. Conflict of interest statement: Z.D. receives research support from Incyte and Regimmune and has received consulting fees from Syndax Pharmaceuticals and Omeros. D.R.C. has received consulting fees from Incyte. And Fresenius and has been a non-promotional speaker for Mallinckrodt Pharmaceuticals. R.Z. received honorarium from Novartis, Incyte and Mallinckrodt. D.W. has served on the advisory boards for Novartis and Incyte; has served on data and safety monitoring boards for Novartis and Behring; and has received honoraria from Takeda, Gilead, Pfizer, and Neovii. K.R.S. has served on the data and safety monitoring board for BMS/Juno and on advisory boards for Jazz, Novartis, and Janssen. S.P. has patent applications (US 20130115232A1 and WO2013066369A3) on “Methods of detection of graft-versus-host disease” licensed to ViaCore-IBT laboratories. Y.I. has served on advisory boards for Novartis, Janssen, and Meiji Seika Pharma. C.S.C. has consulted for and received honoraria from Incyte, Jazz, CareDx, Mesoblast, Syndax, Omeros, and Pfizer. J.A.P. has consulted and served on the advisory boards for Syndax, CTI Biopharma, Amgen, and Regeneron, and has received clinical trial support from Novartis, Amgen, Takeda, Janssen, Johnson & Johnson, Pharmacyclics, Abbvie, CTI Biopharma, and BMS. S.J.L. has received research funding from Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer, Syndax, and Takeda and has served on the steering committee for Incyte. G.S. has served on the advisory boards for Novartis, Incyte, Pharmacyclics, Amgen, and Xenikos. S.S. has served on the advisory board for Rigel Pharmaceuticals. P.J.M. has served on the advisory boards for Mesoblast and Rigel Pharmaceuticals and has received honoraria from Janssen. B.R.B. has served on the advisory boards for Magenta Therapeutics and BlueRock Therapeutics, has received research funding from BlueRock Therapeutics, has served on the steering committee for Kadmon Corporation, and is the co-founder of Tmunity Therapeutics. The remaining authors have no conflicts of interest to report. Authorship statement: Z.D. and D.R.C. contributed equally to this work and should be considered co-first authors. B.R.B. and H.T.G. contributed equally to this work.
Financial disclosure: Funding and implementation of this Consensus Project is made possible through support by the Intramural Program of the National Cancer Institute (NCI) Center for Cancer Research and the NIH Intramural and Extramural Research Programs Institutes and Centers. The opinions expressed are those of the authors and do not represent the position of the NCI, the NIH, or the US Government.
© 2021 The American Society for Transplantation and Cellular Therapy
- Allogeneic hematopoietic cell transplantation
- Chronic graft-versus-host disease
- Initial therapy
- Treatment refractory
- National Institutes of Health (U.S.)
- Hematopoietic Stem Cell Transplantation/adverse effects
- United States
- Clinical Trials as Topic
- Graft vs Host Disease/therapy
- Chronic Disease
PubMed: MeSH publication types
- Research Support, N.I.H., Intramural
- Journal Article