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 Pidala¹, Carrie Kitko², Stephanie J Lee³, Paul Carpenter³, Geoffrey D E Cuvelier⁴, Shernan Holtan⁵, Mary E Flowers³, Corey Cutler⁶, Madan Jagasia⁷, Ted Gooley³, Joycelynne Palmer⁸, Tim Randolph³, John E Levine⁹, Francis Ayuk¹⁰, Fiona Dignan¹¹, Helene Schoemans¹², Eric Tkaczyk¹³, Nosha Farhadfar¹⁴, Anita Lawitschka¹⁵, Kirk R Schultz¹⁶, Paul J Martin³, Stefanie Sarantopoulos¹⁷, Yoshihiro Inamoto¹⁸, Gerard Socie¹⁹, Daniel Wolff²⁰, Bruce Blazar²¹, Hildegard Greinix²², Sophie Paczesny²³, Steven Pavletic²⁴, Geoffrey Hill³

Affiliations

¹ Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. Electronic address: joseph.pidala@moffitt.org.
² Division of Pediatric Hematology/Oncology, Dpeartment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee.
³ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
⁴ Cancer Care Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada.
⁵ Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.
⁶ Division of Stem Cell Transplantation and Cellular Therapy, Dana-Farber Cancer Institute, Boston, Massachusetts.
⁷ Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, Tennessee.
⁸ Division of Biostatistics, Department of Computational and Quantitative Medicine, City of Hope, Duarte, California.
⁹ Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
¹⁰ Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹¹ Department of Clinical Haematology, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester, United Kingdom.
¹² Department of Hematology, University Hospitals Leuven and Department of Public Health, KU Leuven, Leuven, Belgium.
¹³ Department of Veterans Affairs and Departments of Dermatology and Biomedical Engineering, Vanderbilt University Medical Center, Nashville, Tennessee.
¹⁴ Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, Florida.
¹⁵ Stem Cell Transplantation Unit, St Anna Children's Hospital, Medical University of Vienna, Vienna, Austria; Children's Cancer Research Institute, Vienna, Austria.
¹⁶ Pediatric Hematology/Oncology/BMT, BC Children's Hospital, Vancouver, British Columbia, Canada.
¹⁷ Division of Hematological Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University Department of Medicine, Durham, North Carolina.
¹⁸ Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
¹⁹ Hematology and Bone Marrow Transplant Department, AP-HP Saint Louis Hospital and University of Paris, Paris, France.
²⁰ Department of Internal Medicine III, University Hospital of Regensburg, Regensburg, Germany.
²¹ Department of Pediatrics, Division of Blood & Marrow Transplantation & Cellular Therapy, University of Minnesota, Minneapolis, Minnesota.
²² Clinical Division of Hematology, Medical University of Graz, Graz, Austria.
²³ Department of Microbiology and Immunology and Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina.
²⁴ Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

PMID: 33836313
PMCID: PMC8934187
DOI: 10.1016/j.jtct.2021.03.029

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 et al. Transplant Cell Ther. 2021 Aug.

. 2021 Aug;27(8):632-641.

doi: 10.1016/j.jtct.2021.03.029. Epub 2021 Apr 6.

Authors

Affiliations

¹ Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. Electronic address: joseph.pidala@moffitt.org.
² Division of Pediatric Hematology/Oncology, Dpeartment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee.
³ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
⁴ Cancer Care Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada.
⁵ Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.
⁶ Division of Stem Cell Transplantation and Cellular Therapy, Dana-Farber Cancer Institute, Boston, Massachusetts.
⁷ Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, Tennessee.
⁸ Division of Biostatistics, Department of Computational and Quantitative Medicine, City of Hope, Duarte, California.
⁹ Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
¹⁰ Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹¹ Department of Clinical Haematology, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester, United Kingdom.
¹² Department of Hematology, University Hospitals Leuven and Department of Public Health, KU Leuven, Leuven, Belgium.
¹³ Department of Veterans Affairs and Departments of Dermatology and Biomedical Engineering, Vanderbilt University Medical Center, Nashville, Tennessee.
¹⁴ Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, Florida.
¹⁵ Stem Cell Transplantation Unit, St Anna Children's Hospital, Medical University of Vienna, Vienna, Austria; Children's Cancer Research Institute, Vienna, Austria.
¹⁶ Pediatric Hematology/Oncology/BMT, BC Children's Hospital, Vancouver, British Columbia, Canada.
¹⁷ Division of Hematological Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University Department of Medicine, Durham, North Carolina.
¹⁸ Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
¹⁹ Hematology and Bone Marrow Transplant Department, AP-HP Saint Louis Hospital and University of Paris, Paris, France.
²⁰ Department of Internal Medicine III, University Hospital of Regensburg, Regensburg, Germany.
²¹ Department of Pediatrics, Division of Blood & Marrow Transplantation & Cellular Therapy, University of Minnesota, Minneapolis, Minnesota.
²² Clinical Division of Hematology, Medical University of Graz, Graz, Austria.
²³ Department of Microbiology and Immunology and Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina.
²⁴ Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

PMID: 33836313
PMCID: PMC8934187
DOI: 10.1016/j.jtct.2021.03.029

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.

Keywords: Allogeneic hematopoietic cell transplantation; Chronic graft-versus-host disease; Consensus; Preemptive therapy; Risk assignment biomarkers.

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Conflict of interest statement

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).

References

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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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources