The GvHD Hub uses cookies on this website. They help us give you the best online experience. By continuing to use our website without changing your cookie settings, you agree to our use of cookies in accordance with our updated Cookie Policy

Vedolizumab treatment for the prevention of acute GvHD following allogeneic hematopoietic stem cell transplantation

Jan 20, 2020

T cell trafficking to gut-associated lymphoid tissue has been shown to play a key role in acute graft-versus-host disease (aGvHD) establishment in experimental models.1 A key mediator of T-cell adhesion to gut endothelial cells is the integrin α4β1, which binds to mucosal addressin cell adhesion molecule 1 (MAdCAM-1) found specifically on gut endothelial cells.2,3 Vedolizumab, an anti-α4β1 humanized monoclonal antibody, has been shown to elicit gut-specific immunomodulatory activity and is currently approved for the treatment of moderate to severe ulcerative colitis and Crohn’s disease in adults.4

Yi-Bin Chen, Massachusetts General Hospital, Boston, US, and colleagues explored the potential benefits of coadministration of vedolizumab with standard GvHD prophylaxis in a phase Ib, open-label study (NCT02728895).4 The study evaluated the tolerability, safety, pharmacokinetic profile, and efficacy of vedolizumab in 24 patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) and was recently published in Blood Advances.

The GvHD Hub recently covered GvHD prophylaxis as a monthly theme. Read more here.

Study Design


  • All patients underwent either a myeloablative or reduced-intensity conditioning (Table 1) followed by standard GvHD prophylaxis (tacrolimus [recommended goal serum trough concentration of 5–10ng/dL] and MTX [recommended 10 mg/m2IV on Days +1, +3, +6 and +11 after allo-HSCT])
  • Patients received 75 mg (n= 3) or 300 mg (n= 21, dose-escalation) IV vedolizumab, on Days -1, +13, and +42 subsequent to the allo-HSCT procedure
  • Dose escalation:
    • Three participants were primarily enrolled on the 75 mg IV vedolizumab dosing regimen, on Days -1, +13, and +42 after the allo-HSCT procedure
    • If the first patient tolerated the basal dose and reached full neutrophil engraftment, two further participants were enrolled and observed for dose-limiting toxicities (DLTs)
    • A lack of DLTs across three patients resulted in the initiation of a dose-determining phase where additional 21 patients received 300 mg IV vedolizumab


  • Primary endpoints: to identify the tolerability and safety of vedolizumab and determine the recommended dose
  • Secondary endpoints: characterize PK profile of vedolizumab in participants and determine the cumulative incidence and the severity of aGVHD by 100 days after allo-HSCT


  • Patient characteristics
    • Patients (n= 24), median age 55 (range, 18–72) years, undergoing allo-HSCT were recruited (Table 1)

Table 1. Characteristics of study sample defined by vedolizumab dose cohort

Characteristic Vedolizumab 75 mg
(n= 3)
Vedolizumab 300 mg
(n= 21)
Total (N= 24)
Median age, years (range) 22 (18–50­) 58 (19–72) 55 (18–72)
Disease Type      
Myeloproliferative neoplasm 0 3 3
Myelodysplastic/myeloproliferative neoplasm 0 3 3
Myelodysplastic syndrome 0 2 2
AML or related precursor neoplasm 3 6 9
Precursor Lymphoid neoplasm 0 5 5
           Precursor T-ALL/LBL 0 3 3
           Precursor B-ALL/LBL 0 2 2
Other 0 2 2
Conditioning Regimen      
Myeloablative, busulfan + fludarabine 2 5 7
Myeloablative, cyclophosphamide + TBI 1 5 6
Reduced-intensity, busulfan + fludarabine 0 6 6
Reduced-intensity, fludarabine + melphalan 0 5 5
Source of stem cells      
Bone Marrow 3 6 9
Peripheral blood 0 15 15
HLA compatibility      
Matched 3 20 23
Mismatched 0 1 1
Donor relationship to study participant      
Related 0 4 4
Unrelated 3 17 20

B-ALL, B-cell acute lymphoblastic leukemia; HLA, human leukocyte antigen; LBL, lymphoblastic lymphoma; T-ALL, T-cell acute lymphoblastic leukemia; TBI, total body irradiation

  • Safety4
    • All participants experienced at least one grade III or higher TEAE, eight of which were considered related to vedolizumab (n= 2 and n= 6 in the 75 mg and 300 mg dose cohorts, respectively).
    • Serious TEAEs were observed in 13 of 24 participants. However, only in one patient in the 300 mg dose cohort it was considered to be related to study drug
    • No DLTs were observed for participants in either dose cohort
    • Cytomegalovirus- and Clostridium difficile-related infections were the most common TEAEs in the 300 mg dose cohort
    • Neutrophil engraftment was observed by Day +100 for all 24 participants. Time to engraftment was not significantly different between the 300 mg dose cohort (median 14; interquartile range 13–17 days) and the 75 mg dose cohort which saw one patient reaching engraftment at Day 15 and two at Day 22
    • Of the three deaths observed over the course of the study, none were believed to be related to vedolizumab
  • Efficacy
    • No participants in the 75 mg dose cohort developed grade II–IV aGvHD by 100 days post allo-HSCT
    • By Day 100, three of the 21 participants in the 300 mg dose cohort developed grade II aGvHD while one developed grade III acute GvHD (location: two skin only, two skin + intestinal tract, one skin + intestinal tract + liver). Grade I intestinal aGVHD occurred in three participants
    • At 12 months following allo-HSCT, three patients had grade II aGvHD and two patients had grade III aGvHD. However, no further participants developed aGvHD of the lower intestinal tract
    • One of the four deaths observed over the 12-month course of the study was a result of aGvHD
    • In the 300 mg dose cohort at 12 months, the overall survival was 84.7% and non-relapse mortality was 5.6%
  • PK profile
    • Vedolizumab IV at a dose of 300 mg was considered sufficient to maintain good α4β1 saturation. Therefore, no further dose escalation was required


  • Vedolizumab was well tolerated and did not interfere with engraftment when combined with standard GvHD prophylaxis in patients undergoing allo-HSCT
  • Despite the small study size, there were encouraging signs for a low intestinal aGVHD and overall grade III to IV aGVHD
  • The heterogenous nature of clinical characteristics, such as stem cell sources and conditioning intensities, was a further limitation associated with the study
  • Results from this study have justified a phase III randomized study (NCT03657160) investigating the administration of vedolizumab 300mg alongside standard GvHD prophylaxis in patients undergoing allo-HSCT
  1. Murai, M. et al., Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction. Nat Immunol. 2003; 4(2): 154–160. DOI:10.1038/ni879
  2. Ueha, S. et al., Intervention of MAdCAM-1 or fractalkine alleviates graft-versus-host reaction associated intestinal injury while preserving graft-versus-tumor effects. J Leukoc Biol. 2006 Jan; 81(1): 176–185. DOI: 10.1189/jlb.0306231
  3. Waldman E. et al., Absence of beta7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine. Blood. 2006 Feb 15;107(4):1703-1711. DOI: 10.1182/blood-2005-08-3445
  4. Chen Y. et al., Vedolizumab for prevention of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Blood Adv. 2019; 3(23): 4136–4146. DOI: 10.1182/bloodadvances.2019000893