TY - JOUR
T1 - A phase 2 study of interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract
AU - Ponce, Doris M.
AU - Alousi, Amin M.
AU - Nakamura, Ryotaro
AU - Slingerland, John
AU - Calafiore, Marco
AU - Sandhu, Karamjeet S.
AU - Barker, Juliet N.
AU - Devlin, Sean
AU - Shia, Jinru
AU - Giralt, Sergio
AU - Perales, Miguel Angel
AU - Moore, Gillian
AU - Fatmi, Samira
AU - Soto, Cristina
AU - Gomes, Antonio
AU - Giardina, Paul
AU - Marcello, Lee Ann
AU - Yan, Xiaoqiang
AU - Tang, Tom
AU - Dreyer, Kevin
AU - Chen, Jianmin
AU - Daley, William L.
AU - Peled, Jonathan U.
AU - van den Brink, Marcel R.M.
AU - Hanash, Alan M.
N1 - Publisher Copyright:
© 2023 The American Society of Hematology
PY - 2023/3/23
Y1 - 2023/3/23
N2 - 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.
AB - 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.
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U2 - 10.1182/blood.2021015111
DO - 10.1182/blood.2021015111
M3 - Article
C2 - 36399701
AN - SCOPUS:85150064519
SN - 0006-4971
VL - 141
SP - 1389
EP - 1401
JO - Blood
JF - Blood
IS - 12
ER -