Phase III GRAPHITE study of Entyvio meets primary endpoint in acute graft-versus-host disease and data is presented at 2023 Tandem meetings

Intestinal aGvHD is a serious complication characterized by inflammation of the GI tract which can affect patients undergoing allo-HSCT, a common treatment for blood cancers. Vedolizumab is not currently indicated for use in aGvHD.

The Phase III, randomized, double-blind, placebo-controlled, multicenter GRAPHITE study evaluated the efficacy and safety of vedolizumab as prophylaxis for intestinal aGvHD in patients undergoing allo-HSCT from unrelated donors for the treatment of hematological malignancies. The study met its primary endpoint, with vedolizumab achieving a statistically significant improvement in intestinal aGvHD-free survival versus placebo by Day 180 after allo-HSCT (85.5% of patients in the vedolizumab arm versus 70.9% in the placebo arm [HR=0.45; 95% CI: 0.27, 0.73; p<0.001]). statistically significant superiority of vedolizumab over placebo was also demonstrated for intestinal agvhd-free and relapse-free survival by day +180 (hr="0.56," 95% ci: 0.37, 0.86; p="0.0043)," and for grade c-d agvhd-free (with any organ involvement) survival at day +180 (hr: 0.59, 95% ci: 0.39, 0.91; p="0.0204)."

In addition, no relevant differences in safety profile between the vedolizumab and placebo arms were observed, and no new safety signals were identified. Treatment-related adverse events were reported in 24.8% versus 28.4%, and treatment related serious adverse events in 8.5% versus 6.5% of patients treated with placebo versus vedolizumab, respectively. The most common adverse events of special interest were hypersensitivity reactions (placebo 82.4%, vedolizumab 79.3%), serious infections (placebo 67.3%, vedolizumab 74.0%), and liver injury (placebo 41.8%, vedolizumab 40.2%).

Intestinal aGvHD can occur after stem cell transplantation when the immune cells of the donor (the graft) consider the recipient’s body (the host) as foreign and attack the organs and tissue. Intestinal aGvHD results in the majority of morbidity and mortality associated with GvHD. Effective prevention of aGvHD, especially with lower intestinal involvement, has been an important treatment goal for physicians when patients are undergoing allo-HSCT.

GRAPHITE (vedolizumab-3035) is a randomized, double-blind, placebo controlled study designed to evaluate the use of vedolizumab as prophylaxis of intestinal aGvHD in participants who receive allo-HSCT as treatment for a hematologic malignancy or myeloproliferative disorder from an unrelated donor. The study enrolled 333 patients who were randomly assigned in a 1:1 ratio to one of two treatment groups receiving either an intravenous infusion of vedolizumab 300 mg or placebo on days -1 (before allo-HSCT), and on days +13, +41, +69, +97, +125, and +153 following allo-HSCT, alongside a background GvHD prophylaxis regimen. The overall time of participation in the study was 12 months.