A phase 2a randomized clinical trial of intravenous vedolizumab for the treatment of steroid-refractory intestinal acute graft-versus-host disease

• DOI: 10.1038/s41409-021-01356-0
• Publication Date: 2021-06-09T14:21:47Z
• Authors: Yngvar Fløisand; Mark A. Schroeder; Patrice Chevallier; Dominik Selleslag; Steven Devine; Anne S. Renteria; Mohamad Mohty; Ibrahim Yakoub-Agha; Chunlin Chen; Andrejus Parfionovas; Syed Quadri; Johan Jansson; Mona Akbari; Yi-Bin Chen
• Keywords: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology; 0301 basic medicine; Hematopoietic Stem Cell Transplantation; 610; Graft vs Host Disease; [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology; [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology; Drug development; [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy; Antibodies, Monoclonal, Humanized; Graft-versus-host disease; Antibodies; [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology; Article; 3. Good health; 03 medical and health sciences; Molecularly targeted therapy; Monoclonal; Acute Disease; Humans; Steroids; [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy; Humanized

AbstractSteroid-refractory (SR) acute graft-versus-host disease (aGvHD) remains a significant complication after allogeneic hematopoietic cell transplantation. Systemic corticosteroids are first-line therapy for aGvHD, but apart from ruxolitinib, there are no approved treatments for SR aGvHD. Vedolizumab is approved for treatment of ulcerative colitis and Crohn’s disease, and may be effective for treatment of SR intestinal aGvHD. We conducted a phase 2a trial (NCT02993783) to evaluate the clinical efficacy, tolerability, and safety of vedolizumab 300 and 600 mg for SR intestinal aGvHD. This study was terminated before full enrollment was completed because early results failed to demonstrate positive proof-of-concept in efficacy. Before termination, 17 participants had enrolled and an early response in intestinal aGvHD was observed in 11 and eight participants at days 15 and 28, respectively. All adverse events observed were consistent with those expected in a population with SR intestinal aGvHD. Overall, vedolizumab did not meet the primary efficacy endpoint (overall response at day 28), likely owing to premature study drug discontinuation, lack of efficacy, and the competing risks inherent with a population with advanced SR intestinal aGvHD. Nevertheless, this study provides valuable insights into the considerations needed when conducting studies in patients with SR intestinal aGvHD.