A phase 2 study of interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract
Year: 2022
Type: article
Study design: Clinical Trial
Abstract: Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality following allogeneic hematopoietic transplantation. In experimental models, interleukin-22 promotes epithelial regeneration and induces innate antimicrobial molecules. We conducted a multicenter single-arm phase 2 study evaluating the safety and efficacy of a novel recombinant human interleukin-22 dimer, F-652, used in combination with systemic corticosteroids for treatment of newly diagnosed lower gastrointestinal acute GVHD. The most common adverse events were cytopenias and electrolyte abnormalities, and there were no dose-limiting toxicities. Out of 27 patients, 19 (70%; 80% confidence interval, 56%-79%) achieved a day-28 treatment response, meeting the prespecified primary endpoint. Responders exhibited a distinct fecal microbiota composition characterized by expansion of commensal anaerobes, which correlated with increased overall microbial α-diversity, suggesting improvement of GVHD-associated dysbiosis. This work demonstrates a potential approach for combining immunosuppression with tissue-supportive strategies to enhance recovery of damaged mucosa and promote microbial health in patients with gastrointestinal GVHD. This trial was registered at www.clinicaltrials.gov as NCT02406651.
Source: Blood
Authors: Doris M. Ponce, Amin M. Alousi, Ryotaro Nakamura, John Slingerland, Marco Calafiore, Karamjeet S. Sandhu, Juliet N. Barker, Sean Devlin, Jinru Shia, Sergio Giralt, Miguel-Angel Perales, Gillian Moore, Samira Fatmi, Cristina Soto, Antonio Gomes, Paul Giardina, LeeAnn Marcello, Xiaoqiang Yan, Tom Tang, Kevin Dreyer, Jianmin Chen, William L. Daley, Jonathan U. Peled, Marcel R. M. van den Brink, Alan M. Hanash
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Immunobiology of Allogeneic Hematopoietic Cell Transplantation, G2183351267, Microbiota mechanisms and biomarkers in GVHD, The role of bile acid metabolomics in graft-versus-host disease, IL-22 in Thymic Regeneration, Cancer Center Support Grant, T cell invasion of the stem cell compartment during immune-mediated GI damage
OpenAlex ID: W4309353208