A phase 2 study of interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract
Doris M. Ponce, Amin M. Alousi, Ryotaro Nakamura, John Slingerland, Marco Calafiore, Karamjeet Sandhu, Juliet N. Barker, Sean Devlin, Jinru Shia, Sergio Giralt, Miguel‐Angel Perales, Gillian Moore, Samira Fatmi, Cristina Crespo Soto, Antonio L. C. 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
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.