Teduglutide for treatment-refractory severe intestinal acute graft-versus-host disease - a multicenter survey
Intestinal glucocorticoid-refractory (SR) acute (a) graft-versus-host disease (GVHD) causes high non-relapse mortality (NRM) in patients after allogeneic hematopoietic cell transplantation (allo-HCT). Recent preclinical data indicate that acute GVHD causes a loss of intestinal neuroendocrine L-cells leading to reduced levels of glucagon-like peptide-2 (GLP-2). GLP-2 substitution improved GVHD severity and increased Paneth cells and intestinal stem cells in mice. This motivated us to treat patients with refractory intestinal aGHVD using the GLP-2-analogon teduglutide. In this retrospective multicenter survey, 17 patients received teduglutide as salvage-therapy for SR-intestinal aGVHD. The best response (CR or PR) at any time point during and after treatment was 64.7% (11/17) including 41.2% (7/17) CR and 23.5% (4/17) PR. At a median follow-up of 28 weeks after teduglutide 10/17 patients are alive. Most patients experienced an increase of the albumin serum level within 2 months after the first teduglutide dose, including patients who clinically did not respond to teduglutide treatment. No specific teduglutide-related toxicity was observed. Our retrospective analysis suggests that teduglutide is safe and has activity in a fraction of patients with intestinal SR-aGVHD, which needs validation in a prospective trial.
Authors
- Francesca Biavasco (ORCID: https://orcid.org/0000-0002-8582-2227)
- Gèrard Socié (ORCID: https://orcid.org/0000-0002-2114-7533)
- Rakefet Sidlik Muskatel (ORCID: https://orcid.org/0000-0002-1406-0165)
- Gabriele Ihorst (ORCID: https://orcid.org/0000-0002-8091-1589)
- Jürgen Finke (ORCID: https://orcid.org/0000-0002-1799-5927)
- Johannes Jung (ORCID: https://orcid.org/0000-0003-0137-7929)
- David Michonneau (ORCID: https://orcid.org/0000-0003-4553-3065)
- Kristina Maas‐Bauer (ORCID: https://orcid.org/0000-0003-1788-2807)
- Mareike Verbeek
- Claudia Wehr (ORCID: https://orcid.org/0000-0002-5037-6175)
- Johannes Clausen (ORCID: https://orcid.org/0000-0002-2729-9706)
- Robert Zeiser (ORCID: https://orcid.org/0000-0001-6565-3393)
- Ralph Wäsch (ORCID: https://orcid.org/0000-0002-0813-3444)
- Lohith Gowda (ORCID: https://orcid.org/0009-0001-1726-9749)
- Stuart Seropian
- Régis Peffault de Latour
- Niklas Brehm
- Christoph Nuernbergk (ORCID: https://orcid.org/0009-0001-6001-0601)
Institutions
- Inserm (FR)
- University of Freiburg (DE)
- Université Paris Cité (FR)
- University Medical Center Freiburg (DE)
- Acute Leukemia French Association (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Schneider Children's Medical Center (IL)
- Krankenhaus der Elisabethinen (AT)
- Hôpital Saint-Louis (FR)
- Smilow Cancer Hospital (US)
- Technical University of Munich (DE)
Publication Details
- Journal
- Bone Marrow Transplantation
- Published
- 2025-04-14
- DOI
- https://doi.org/10.1038/s41409-025-02586-2
- Citations
- 3
- Primary Topic
- Hematopoietic Stem Cell Transplantation
- Type
- article
- Field-Weighted Citation Impact
- 5.31
Funders
- Leukemia and Lymphoma Society
- European Commission
- Deutsche Forschungsgemeinschaft
- José Carreras Leukämie-Stiftung
- Deutsche Krebshilfe