Phase II, Open-Label Clinical Trial of Urinary-Derived Human Chorionic Gonadotropin/Epidermal Growth Factor for Life-Threatening Acute Graft-versus-Host Disease

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Treatments that aid inflammation resolution, immune tolerance, and epithelial repair may improve outcomes beyond high-dose corticosteroids and other broad immunosuppressants for life-threatening acute graft-versus-host disease (aGVHD). We studied the addition of urinary-derived human chorionic gonadotropin/epidermal growth factor (uhCG/EGF; Pregnyl; Organon, Jersey City, NJ) to standard aGVHD therapy in a prospective Phase II clinical trial ( identifier NCT02525029). Twenty-two patients with Minnesota (MN) high-risk aGVHD received methylprednisolone 48 mg/m2/day plus 2000 units/m2 of uhCG/EGF s.c. every other day for 1 week. Patients requiring second-line aGVHD therapy received uhCG/EGF 2000 to 5000 units/m2 s.c. every other day for 2 weeks plus standard of care immunosuppression (physician's choice). Responding patients were eligible to receive maintenance doses twice weekly for 5 weeks. Immune cell subsets in peripheral blood were evaluated by mass cytometry and correlated with plasma amphiregulin (AREG) level and response to therapy. Most patients had stage 3-4 lower gastrointestinal tract GVHD (52%) and overall grade III-IV aGVHD (75%) at time of enrollment. The overall proportion of patients with a response at day 28 (primary endpoint) was 68% (57% with complete response, 11% with partial response). Nonresponders had higher baseline counts of KLRG1+ CD8 cells and T cell subsets expressing TIM-3. Plasma AREG levels remained persistently elevated in nonresponders and correlated with AREG expression on peripheral blood T cells and plasmablasts. The addition of uhCG/EGF to standard therapy is a feasible supportive care measure for patients with life-threatening aGVHD. As a commercially available, safe, and inexpensive drug, uhCG/EGF added to standard therapy may reduce morbidity and mortality from severe aGVHD and merits further study.

Original languageEnglish (US)
Pages (from-to)509.e1-509.e8
JournalTransplantation and Cellular Therapy
Issue number8
StatePublished - Aug 2023

Bibliographical note

Funding Information:
Conflict of interest statement: S.G.H. reports clinical trial adjudication for CSL Behring and receipt of research funding from Vitrac Therapeutics and Incyte. J.M. reports research funding from Gilead, CRISPR Therapeutics, Precision BioSciences, Scripps, Fate Therapeutics, and ADC Therapeutics. B.C.B. reports patents and royalties (WO2019165156) and honoraria from CTI Biopharma and honoraria from Incyte. J.S.M. reports receipt of honoraria and membership on the board of directors or an advisory committee for ONK Therapeutics, consultancy and stock options for Vycellix, and consultancy for, stock options with, and research funding from GT Biopharma and Fate Therapeutics. J.E.W. reports consultancy for ASC Therapeutics, bluebird bio, Vertex Pharmaceuticals, and Magenta Therapeutics and consultancy for and equity holding in Rocket Pharmaceuticals. D.J.W.: reports research support from Fate Therapeutics and Incyte. The other authors have no conflicts of interest to disclose.

Funding Information:
Financial disclosure: This study was completed using grant funding from Regenerative Medicine Minnesota (to S.G.H.) and the University of Minnesota Department of Medicine (to S.G.H.) . No funding from the pharmaceutical industry was used to support this study.

Publisher Copyright:
© 2023 The American Society for Transplantation and Cellular Therapy


  • Amphiregulin
  • GVHD
  • Tissue repair
  • Tolerance

PubMed: MeSH publication types

  • Clinical Trial, Phase II
  • Journal Article
  • Research Support, Non-U.S. Gov't


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