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. 2021 Sep;27(9):729-737.
doi: 10.1016/j.jtct.2021.05.004. Epub 2021 Jun 11.

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. The 2020 Treatment of Chronic GVHD Report

Zachariah DeFilipp  1 , Daniel R Couriel  2 , Aleksandr Lazaryan  3 , Vijaya Raj Bhatt  4 , Nataliya P Buxbaum  5 , Amin M Alousi  6 , Attilio Olivieri  7 , Drazen Pulanic  8 , Joerg P Halter  9 , Lori A Henderson  10 , Robert Zeiser  11 , Ted A Gooley  12 , Kelli P A MacDonald  13 , Daniel Wolff  14 , Kirk R Schultz  15 , Sophie Paczesny  16 , Yoshihiro Inamoto  17 , Corey S Cutler  18 , Carrie L Kitko  19 , Joseph A Pidala  3 , Stephanie J Lee  20 , Gerard Socie  21 , Stefanie Sarantopoulos  22 , Steven Z Pavletic  23 , Paul J Martin  20 , Bruce R Blazar  24 , Hildegard T Greinix  25
Affiliations

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. The 2020 Treatment of Chronic GVHD Report

Zachariah DeFilipp et al. Transplant Cell Ther. 2021 Sep.

Abstract

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.

Keywords: Allogeneic hematopoietic cell transplantation; Chronic graft-versus-host disease; Consensus; Initial therapy; Treatment refractory.

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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.
Pathophysiologic pathways interface between clinical manifestations and biological profiles of patients with chronic GVHD at time point 0 (T0, prior to treatment start or change) and time point 1 (T1, following treatment). The goal of the proposed chronic GVHD clinical study design is to determine the association between these 3 essential elements–clinical manifestations, biomarker profile, pathophysiologic inferences–and how they change from T0 to T1.
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References

    1. Socié G, Ritz J. Current issues in chronic graft-versus-host disease. Blood 2014;124:374–384. - PMC - PubMed
    1. Inamoto Y, Storer BE, Lee SJ, et al. Failure-free survival after second-line systemic treatment of chronic graft-versus-host disease. Blood 2013;121:2340–2346. - PMC - PubMed
    1. Inamoto Y, Flowers MED, Sandmaier BM, et al. Failure-free survival after initial systemic treatment of chronic graft-versus-host disease. Blood 2014;124:1363–1371. - PMC - PubMed
    1. Pidala J, Martens M, Anasetti C, et al. Factors associated with successful discontinuation of immune suppression after allogeneic hematopoietic cell transplantation. JAMA Oncol 2020;6: e192974. - PMC - PubMed
    1. Martin PJ, Lee SJ, Przepiorka D, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. The 2014 Clinical Trial Design Working Group report. Biol Blood Marrow Transplant 2015;21:1343–1359. - PMC - PubMed

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