aGvHD

Vedolizumab for the treatment of steroid-resistant severe intestinal acute graft-versus-host disease

Ivetta Danylesko and colleagues conducted a multi-center study evaluating the use of vedolizumab  in severe steroid resistant (SR) gatrointestinal (GI) graft-versus-host disease (GvHD). SR aGvHD is a life-threating complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). vedolizumab is a gut-selective integrin blocker that targets the binding of integrin α4β7 to Mad CAM-1, blocking the homing of T cells to the GI endothelium and thus it may be beneficial for the treatment of intestinal GvHD. The results of the study were published ahead of print in Bone Marrow Transplantation.

Patients and methods:
  • N = 29
  • Median age = 55 years (range, 19–67)
  • Early treatment group: 45% of patients received vedolizumab as second line of treatment
  • Late treatment group: 55% of patients received vedolizumab after ≥ third lines of therapy
  • SR GI aGvHD was defined as progressive/refractory disease failing methylprednisolone at a dose of 1–2 mg/kg
  • Vedolizumab was administered at a dose of 300 mg IV, with planned repeated infusion at 2, 6 and every 8 weeks from then on
  • Eleven patients also had liver and skin aGvHD
Key findings:
  • Response rates in the early and late treatment groups:
    • ORR (CR+PR) = 100% (13/13) vs5% (10/16), P = 0.012
    • CR rate = 53.8% (7/13) vs25% (1/16), P = 0.047
  • 6-month overall survival rate = 46% vs5%, P = 0.047
  • The early treatment group had a higher chance of being off immunosuppression: 69.2% (9/13) vs8% (3/16), P = 0.007
  • The early treatment group had less fatal infectious complications: 38.5% (5/13) vs5% (14/16), P = 0.006

The authors concluded by stating that their findings suggest that targeting integrin α4β7 may improve severe SR GI aGvHD, especially when vedolizumab is started early, as second line treatment after steroids failure. They further added that “the timing, role, and safety of vedolizumab should be further explored in prospective clinical trials.”

References
  1. Danylesko I. et al. Anti-α4β7 integrin monoclonal antibody (vedolizumab) for the treatment of steroid-resistant severe intestinal acute graft-versus-host disease. Bone Marrow Transplant. 2018 Oct 24. DOI: 10.1038/s41409-018-0364-5. [Epub ahead of print].
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