Journal Article

Vedolizumab for the prevention of intestinal acute GVHD after allogeneic hematopoietic stem cell transplantation: a randomized phase 3 trial

Rossiter, Guillermo, Fløisand, Yngvar, Zeiser, Robert, Chen, Yi-Bin, Chen, Jingjing, Jansson, Johan, Maertens, Johan, Mohty, Mohamad, Jamy, Omer, Teshima, Takanori, Cao, Hong, Purtill, Duncan

2024

Overview

Acute graft-versus-host disease (aGVHD) of the lower gastrointestinal (GI) tract is a major cause of morbidity and mortality in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). Vedolizumab is a gut-selective anti-α 4 β 7 integrin monoclonal antibody that reduces gut inflammation by inhibiting migration of GI-homing T lymphocytes. The efficacy and safety of vedolizumab added to standard GVHD prophylaxis (calcineurin inhibitor plus methotrexate/mycophenolate mofetil) was evaluated for prevention of lower-GI aGVHD after unrelated donor allo-HSCT in a randomized, double-blind, placebo-controlled phase 3 trial. Enrollment closed early during the COVID-19 pandemic with 343 patients randomized ( n  = 174 vedolizumab, n  = 169 placebo), and 333 received ≥1 intravenous dose of 300 mg vedolizumab ( n  = 168) or placebo ( n  = 165) and underwent allo-HSCT. The primary end point was met; Kaplan–Meier (95% confidence interval) estimated rates of lower-GI aGVHD-free survival by day +180 after allo-HSCT were 85.5% (79.2–90.1) with vedolizumab versus 70.9% (63.2–77.2) with placebo (hazard ratio, 0.45; 95% confidence interval, 0.27–0.73; P  < 0.001). For the 5 key secondary efficacy end points analyzed by day +180 after allo-HSCT, rates of lower-GI aGVHD-free and relapse-free survival and grade C–D aGVHD-free survival were significantly higher with vedolizumab versus placebo. No significant treatment differences were found for the other key secondary end points of non-relapse mortality, overall survival and grade B–D aGVHD-free survival, respectively. Incidence of treatment-related serious adverse events analyzed in patients receiving ≥1 dose of study treatment ( n  = 334) was 6.5% ( n  = 11 of 169) vedolizumab versus 8.5% ( n  = 14 of 165) placebo. When added to standard calcineurin inhibitor-based GVHD prevention, lower-GI aGVHD-free survival was significantly higher with vedolizumab versus placebo. ClinicalTrials.gov identifier: NCT03657160 . In a randomized, double-blind phase 3 trial, the anti-α 4 β 7 integrin monoclonal antibody vedolizumab plus standard prophylaxis was superior to placebo plus prophylaxis for prevention of lower gastrointestinal acute graft-versus-host disease in patients following allogeneic hematopoietic stem cell transplantation.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 692/308/2779/777 / 692/699/249/1529 / Acute Disease / Adolescent / Adult / Aged / Allografts / Antibodies, Monoclonal, Humanized - administration & dosage / Antibodies, Monoclonal, Humanized - adverse effects / Antibodies, Monoclonal, Humanized - therapeutic use / Biomedical and Life Sciences / Biomedicine / Calcineurin inhibitors / Cancer Research / COVID-19 / Digestive system / Disease prevention / Double-Blind Method / Effectiveness / Female / Gastrointestinal tract / Graft versus host disease / Graft vs Host Disease - drug therapy / Graft vs Host Disease - prevention & control / Graft-versus-host reaction / Hematopoietic Stem Cell Transplantation - adverse effects / Hematopoietic stem cells / Homing behavior / Humans / Infectious Diseases / Inhibitors / Leukocyte migration / Lymphocytes / Lymphocytes T / Male / Metabolic Diseases / Methotrexate / Middle Aged / Molecular Medicine / Monoclonal antibodies / Morbidity / Mortality / Mycophenolate mofetil / Mycophenolic acid / Neurosciences / Pandemics / Placebos / Stem cell transplantation / Stem cells / Survival / Transplantation / Transplantation, Homologous - adverse effects / Young Adult