Dr. Chen on the Efficacy of Vedolizumab Prophylaxis for aGVHD in the GRAPHITE Trial

Yi-Bin Chen, director, Hematopoietic Cell Transplant and Cellular Therapy Program, Allen B. Rogers, Jr. and Cara J. Rogers Endowed Chair, instructor, Medical Oncology, Massachusetts General Hospital, associate professor of medicine, Harvard Medical School, discusses key data with the use of vedolizumab (Entyvio) in lower gastrointestinal (GI) acute graft-vs-host disease (aGVHD), according to the phase 3 GRAPHITE Study (NCT03657160).

Vedolizumab is a gut-selective, anti-lymphocyte trafficking humanized monoclonal antibody commonly used to reduce inflammation and damage in the GI tract. The randomized, placebo-controlled GRAPHITE study investigated the efficacy and safety of this agent in preventing the development of any-stage GVHD or death when added to a standard GVHD prophylaxis regimen of calcineurin inhibitor plus methotrexate, Chen begins. The regimen was administered to patients 12 years or older with lower GI aGVHD and hematologic malignancies, who were undergoing their first allogenic hematopoietic stem-cell transplantation (allo-HSCT) from unrelated donors to treat patients.

The trial's primary end point was lower GI aGVHD-free survival 6 months following allogeneic stem cell transplantation, he continues. The study was originally designed to enroll about 558 patients, but closed prematurely due to COVID-19-related factors, Chen notes. Overall, 333 patients were enrolled and randomly assigned to the experimental treatment vs placebo.

Results showed that the vedolizumab-containing regimen met its primary end point, Chen states, adding that the aGVHD-free survival rate with the experimental regimen was 85.5% at day 180 vs 70.9% with the placebo regimen. The hazard ratio was 0.45, indicating that this rate was statistically significant and clinically meaningful, Chen explains. Moreover, vedolizumab showed superiority over placebo for the secondary end points of intestinal aGvHD-free and relapse-free survival at day 180. The incidence of lower GI GVHD was greatly reduced in patients receiving vedolizumab, Chen adds. No new safety signals were identified, and there were no relevant toxicity differences between treatment arms.