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

18 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
Pages (from-to)632-641
Number of pages10
JournalTransplantation and Cellular Therapy
Volume27
Issue number8
DOIs
StatePublished - Aug 2021

Keywords

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

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