A phase 2 study of interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract Journal Article
| Authors: | Ponce, D. M.; Alousi, A. M.; Nakamura, R.; Slingerland, J.; Calafiore, M.; Sandhu, K. S.; Barker, J. N.; Devlin, S.; Shia, J.; Giralt, S.; Perales, M. A.; Moore, G.; Fatmi, S.; Soto, C.; Gomes, A.; Giardina, P.; Marcello, L.; Yan, X.; Tang, T.; Dreyer, K.; Chen, J.; Daley, W. L.; Peled, J. U.; van den Brink, M. R. M.; Hanash, A. M. |
| Article Title: | A phase 2 study of interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract |
| 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. © 2023 The American Society of Hematology |
| Keywords: | clinical trial; phase 2 clinical trial; hematopoietic stem cell transplantation; multicenter study; graft versus host reaction; corticosteroid; graft vs host disease; interleukin-22; adverse event; adrenal cortex hormones; lower gastrointestinal tract; humans; human; eflepedocokin alfa |
| Journal Title: | Blood |
| Volume: | 141 |
| Issue: | 12 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2023-03-23 |
| Start Page: | 1389 |
| End Page: | 1401 |
| Language: | English |
| DOI: | 10.1182/blood.2021015111 |
| PUBMED: | 36399701 |
| PROVIDER: | scopus |
| PMCID: | PMC10163318 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK authors: Doris M. Ponce and Alan Hanash -- Source: Scopus |
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