A phase 2 study of interleukin-22 and systemic corticosteroids as initial treatment for acute GVHD of the lower GI tract

Author:

Ponce Doris M.12ORCID,Alousi Amin M.3,Nakamura Ryotaro4ORCID,Slingerland John5,Calafiore Marco1,Sandhu Karamjeet S.4,Barker Juliet N.12,Devlin Sean6,Shia Jinru7ORCID,Giralt Sergio12ORCID,Perales Miguel-Angel12ORCID,Moore Gillian1,Fatmi Samira1,Soto Cristina1,Gomes Antonio5ORCID,Giardina Paul5,Marcello LeeAnn5ORCID,Yan Xiaoqiang8,Tang Tom8,Dreyer Kevin8,Chen Jianmin8,Daley William L.8,Peled Jonathan U.12ORCID,van den Brink Marcel R. M.125,Hanash Alan M.129

Affiliation:

1. 1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY

2. 2Department of Medicine, Weill Cornell Medical College; New York, NY

3. 3Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX

4. 4Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope National Medical Center, Duarte, CA

5. 5Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY

6. 6Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY

7. 7Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY

8. 8Evive Biotechnology (Shanghai) Ltd (formerly Generon [Shanghai] Corporation Ltd), Shanghai, China

9. 9Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY

Abstract

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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference62 articles.

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4. A refined risk score for acute graft-versus-host disease that predicts response to initial therapy, survival, and transplant-related mortality;MacMillan;Biol Blood Marrow Transplant,2015

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