作者
Doris M. Ponce,Amin M. Alousi,Ryotaro Nakamura,John Slingerland,Marco Calafiore,Karamjeet S. Sandhu,Juliet N. Barker,Sean M. Devlin,Jinru Shia,Sergío Giralt,Miguel-Ángel Perales,Gillian Moore,Samira Fatmi,Cristina Soto,António Gomes,Paul A. Giardina,LeeAnn T. Marcello,Xiaoqiang Yan,Tom Tang,K. Dreyer,Jianmin Chen,William Daley,Jonathan U. Peled,Marcel R.M. van den Brink,Alan M. Hanash
摘要
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.