National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IIb. The 2020 Preemptive Therapy Working Group Report

Joseph Pidala, Carrie Kitko, Stephanie J. Lee, Paul Carpenter, Geoffrey D.E. Cuvelier, Shernan Holtan, Mary E. Flowers, Corey Cutler, Madan Jagasia, Ted Gooley, Joycelynne Palmer, Tim Randolph, John E. Levine, Francis Ayuk, Fiona Dignan, Helene Schoemans, Eric Tkaczyk, Nosha Farhadfar, Anita Lawitschka, Kirk R. SchultzPaul J. Martin, Stefanie Sarantopoulos, Yoshihiro Inamoto, Gerard Socie, Daniel Wolff, Bruce Blazar, Hildegard Greinix, Sophie Paczesny, Steven Pavletic, Geoffrey Hill

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Chronic graft-versus-host disease (GVHD) commonly occurs after allogeneic hematopoietic cell transplantation (HCT) despite standard prophylactic immune suppression. Intensified universal prophylaxis approaches are effective but risk possible overtreatment and may interfere with the graft-versus-malignancy immune response. Here we summarize conceptual and practical considerations regarding preemptive therapy of chronic GVHD, namely interventions applied after HCT based on evidence that the risk of developing chronic GVHD is higher than previously appreciated. This risk may be anticipated by clinical factors or risk assignment biomarkers or may be indicated by early signs and symptoms of chronic GVHD that do not fully meet National Institutes of Health diagnostic criteria. However, truly preemptive, individualized, and targeted chronic GVHD therapies currently do not exist. In this report, we (1) review current knowledge regarding clinical risk factors for chronic GVHD, (2) review what is known about chronic GVHD risk assignment biomarkers, (3) examine how chronic GVHD pathogenesis intersects with available targeted therapeutic agents, and (4) summarize considerations for preemptive therapy for chronic GVHD, emphasizing trial development, including trial design and statistical considerations. We conclude that robust risk assignment models that accurately predict chronic GVHD after HCT and early-phase preemptive therapy trials represent the most urgent priorities for advancing this novel area of research.

Original languageEnglish (US)
Pages (from-to)632-641
Number of pages10
JournalTransplantation and Cellular Therapy
Volume27
Issue number8
DOIs
StatePublished - Aug 1 2021

Bibliographical note

Funding Information:
The authors thank the Meredith Cowden GVHD Foundation, France Lymphome Espoir, NBMTLink, Anthony Nolan, the National Marrow Donor Program, BMT InfoNet, and other patient advocacy groups and individual patients for partnering and collaboration on this project. They also thank all the working group and consensus conference participants, professional societies, US government agencies, and all stakeholders in the field of hematopoietic stem cell transplantation nationally and internationally for the generous donation of their work, time, talents, and expertise towards the success of this project. Special thanks to the independent external peer reviewers who provided the comments and critiques to the 2020 NIH Chronic GVHD Consensus Project: Nicolaus Kröger, MD, Professor and Clinical Director, Department of Stem Cell Transplantation, University of Hamburg, Hamburg, Germany and President of the EBMT; Ryotaro Nakamura, MD, Professor and Director of the Center for Stem Cell Transplantation, City of Hope Cancer Center, Duarte, CA; John DiPersio, MD, PhD, Chief of the Division of Oncology, Director of the Center for Gene and Cellular Immunotherapy, and Deputy Director of the Siteman Cancer Center, Washington University School of Medicine, St Louis, MO; Mark Juckett, MD, Professor and Director of the Blood and Marrow Transplant Program, University of Wisconsin, Madison, WI; George Chen, MD, Associate Professor of Medicine, University at Buffalo, Buffalo, NY; Rafael Duarte, MD, PhD, FRCP, Head of the Department of Hematology and Director of the Hematopoietic Transplant Program, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain; Franco Locatelli, MD, Professor of Pediatrics, Università Sapienza and Head of the Department of Pediatric Hematology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy; Areej El-Jawahri, MD, Associate Professor, Director of the Bone Marrow Transplant Survivorship Program, and Associate Director of the Cancer Outcomes Research and Education Program, Massachusetts General Hospital, Boston, MA; Robert Soiffer, MD, Professor, Chief of the Division of Hematologic Malignancies, Chair of the Executive Committee for Clinical Programs, Vice Chair for the Department of Medical Oncology, Chief of the Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA; Daniel Weisdorf, MD, Professor of Medicine and Deputy Director of the Clinical Science and Translational Science Institute and Director of Clinical and Translational Research Services, University of Minnesota, Minneapolis, MN; Keith Sullivan. MD, Professor of Medicine, Hematologic Malignancies, and Cellular Therapy, Duke University Medical Center, Durham, NC; Catherine Lee, MD, Assistant Professor, Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Jose Antonio Perez-Simon, MD, Professor of Hematology, University of Seville, Head of the Department of Hematology, University Hospital Virgen del Rocio, and Vice Director of the Biomedical Research Institute of Seville, Seville, Spain; Doris Ponce, MD, Associate Professor of Medicine, Hematologic Oncologist, Memorial Sloan Kettering Cancer Center, New York, NY; Andrew Harris, MD, Pediatric Hematologist-Oncologist and Assistant Professor of Pediatrics, Pediatric BMT and Cellular Therapy Program, University of Utah/Primary Children's Hospital, Salt Lake City, UT. Financial disclosure: Funding and implementation of this project was made possible through support from the Intramural Program of the National Cancer Institute's 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 National Cancer Institute, the NIH, or the United States Government. Conflict of interest statement: J.P.: consulting and advisory board membership (Syndax, CTI Biopharma, Amgen, Regeneron), clinical trial support (Novartis, Amgen, Takeda, Janssen, Johnson and Johnson, Pharmacyclics, Abbvie, CTI Biopharma, BMS); S.J.L.: clinical trial support (Amgen, AstraZeneca, Incyte, Kadmon, Novartis, Pfizer Syndax, Takeda), steering committee (Incyte); P.C.: research funding (Pharmacyclics); S.H.: consulting (Incyte, Generon); M.E.D.F.: research support (Pharmacyclics, Incyte), speaker honorarium (Janssen, Johnson & Johnson, Mallinckrodt); C.C.: consulting/honoraria (Incyte, Jazz, CareDx, Mesoblast, Syndax, Omeros, Pfizer); M.J.: Iovance employee, leadership position, stock options; T.G.: Data and Safety Monitoring Board member (Pharmacyclics, Kiadis), consultant (Regimmune, Swedish Hospital); F.D.: speaker fees (Janssen, Jazz, Pfizer, Novartis, Mallinckrodt), advisory board (Jazz, Kiadis), travel grants (Jazz); H.S.: advisory board (Incyte, Janssen, Novartis), speaker fees (Novartis, Incyte, Jazz Pharmaceuticals, Takeda, Belgian Hematological Society), travel grants (Abbvie, Celgene, CIBMTR, EBMT, Gilead, Incyte), research funding (Novartis, BHS); E.T.: consultancy fees (Incyte Corporation); N.F.: advisory board (Incyte), research funding (CSL Bearing); P.J.M.: advisory board (Mesoblast, Rigel Pharmaceuticals), honoraria (Janssen); S.S.: advisory board (Rigel Pharmaceuticals); Y.I.: advisory board (Novartis, Janssen, Meiji Seika Pharma); B.B.: advisor (Magenta Therapeutics, BlueRock Therapeutics), research funding (BlueRock Therapeutics, Rheos Medicines), cofounder of Tmunity Therapeutics; G.S.: advisory board (Novartis, Incyte, Pharmacyclics, Amgen, Xenikos); G.R.H.: consulting (Generon Corporation, NapaJen Pharma); research funding (Roche, Compass Therapeutics, Syndax Pharmaceuticals, Applied Molecular Transport, iTeos Therapeutics). Financial disclosure: See Acknowledgments on page 639.

Funding Information:
Financial disclosure: Funding and implementation of this project was made possible through support from the Intramural Program of the National Cancer Institute's 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 National Cancer Institute, the NIH, or the United States Government.

Publisher Copyright:
© 2021

Keywords

  • Allogeneic hematopoietic cell transplantation
  • Chronic graft-versus-host disease
  • Consensus
  • Preemptive therapy
  • Risk assignment biomarkers

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