Vedolizumab for the prevention of lower-GI aGvHD: Results from a phase III trial

A phase III trial (NCT03657160) assessed the safety and efficacy of the addition of vedolizumab, an anti-α4β7 humanized monoclonal antibody, vs placebo to standard graft-versus-host disease (GvHD) prophylaxis following unrelated donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the prevention of lower-gastrointestinal (GI) acute GvHD (aGvHD) in patients aged ≥12 years (n=333).¹ Results from this trial were published in Nature Medicine by Chen, et al.¹ 

The primary endpoint was met; the addition of vedolizumab to standard GvHD prophylaxis improved lower-GI aGvHD-free survival by Day +180 post-allo-HSCT vs placebo (Kaplan-Meier [KM] estimated survival, 85.5% vs 70.9%; p < 0.001), highlighting its potential to reduce early transplant-related complications.

The safety assessment showed that vedolizumab was generally well-tolerated, with no new safety signals, and no clinically relevant differences in adverse events between treatment groups, supporting its use as an adjunct treatment in the allo-HSCT setting​. 

Secondary efficacy endpoints of lower-GI aGvHD-free and relapse of the underlying malignancy-free survival by Day +180 (KM estimated survival, 78.9% vs 65.4%) and International Bone Marrow Transplant Registry Database (IBMTR) Grade C–D aGvHD-free survival by Day +180 (KM estimated survival, 78.9% vs 67.7%) were also favorably impacted by vedolizumab vs placebo.

Incorporating vedolizumab into GvHD prophylaxis protocols could improve patient outcomes post-allo-HSCT by mitigating the incidence and severity of lower-GI aGvHD, ultimately enhancing survival rates and quality of life for transplant recipients. These findings highlight the potential role of vedolizumab in improving the therapeutic landscape of GvHD management, particularly given the lack of specific gut-targeted prophylactic therapies.