GVHD
Published on September 13, 2024
Vedolizumab for the prevention of intestinal acute GVHD after allogeneic hematopoietic stem cell transplantation: a randomized phase 3 trial
by Alex Kadhim
Researchers at various academic institutions, in collaboration with Takeda Pharmaceuticals, have conducted a randomized phase 3 trial to evaluate the efficacy of vedolizumab, a gut-selective anti-α4β7 integrin monoclonal antibody, in preventing lower gastrointestinal (GI) acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The trial was conducted as a double-blind, placebo-controlled study involving 343 patients who were randomized to receive either vedolizumab or placebo in addition to standard GVHD prophylaxis.
The study aimed to assess whether adding vedolizumab to the standard GVHD prophylaxis (calcineurin inhibitor plus methotrexate or mycophenolate mofetil) would improve outcomes for patients receiving unrelated donor allo-HSCT, particularly by reducing the incidence of lower-GI aGVHD. Patients received intravenous doses of vedolizumab or placebo on a set schedule before and after transplantation. The primary endpoint was the lower-GI aGVHD-free survival rate by day 180 after allo-HSCT. Key secondary endpoints included lower-GI aGVHD-free and relapse-free survival, overall survival, and incidence of severe aGVHD of any organ.
Overall, vedolizumab significantly improved lower-GI aGVHD-free survival, with 85.5% of patients in the vedolizumab group remaining free of lower-GI aGVHD by day 180 compared to 70.9% in the placebo group. The hazard ratio for a lower-GI aGVHD event or death was 0.45, indicating a 55% reduction in risk with vedolizumab. Additionally, vedolizumab demonstrated significant benefits in lower-GI aGVHD-free and relapse-free survival, with survival rates of 78.9% for vedolizumab and 65.4% for placebo. Serious adverse events were similar between the groups, with 71% in the vedolizumab group and 69.1% in the placebo group. Therefore, the authors concluded that, when vedolizumab is added to standard GVHD prophylaxis, there is a significant reduction in the incidence of lower-GI aGVHD and improvement in overall patient outcomes without introducing new safety concerns.
Reference:
Chen YB, Mohty M, Zeiser R, et al. Vedolizumab for the prevention of intestinal acute GVHD after allogeneic hematopoietic stem cell transplantation: a randomized phase 3 trial. Nat Med. Published online June 6, 2024.
https://doi.org/10.1038/s41591-024-03016-4
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