aGvHD

EBMT 2018 | Vedolizumab for the treatment of steroid-resistant severe intestinal aGvHD

On Wednesday 21 March 2018 during an oral abstract session at the 44th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT), Arnon Nagler on behalf of his colleagues, presented results of a multi-center study with the use of vedolizumab (Vd) in severe steroid resistant (SR) gatrointestinal (GI) GvHD.

Professor Nagler started his talk by introducing Vd and highlighted its importance in steroid resistant aGvHD which is a life-threating complication of allogeneic-stem cell transplantation (allo-SCT). Vd 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.

Patients and methods:
  • N = 27 patients
  • Median age = 55 years (range, 19–67)
  • Early treatment group (n = 11): received Vd as a second line of treatment
  • Late treatment group (n = 16): received Vd after ≥ third lines of therapy
  • SR GI aGvHD was defined as progressive/refractory disease failing methylprednisolone at a dose of 2 mg/kg
  • Vd was administered at a dose of 300 mg IV, with planned repeated infusion at 2, 6 and every 8 weeks from then on
  • Donors were:
    • unrelated (matched = 19; mismatched = 3)
    • siblings (n = 5)
  • Graft source was: peripheral blood in 24/27 pts
  • Most pts received myeloablative conditioning regimens (n=18)
  • GvHD prophylaxis included Cyclosporin (n=26) or Tacrolimus (n=1) and Methotrexate (n=21) or Mycophenolate Mofetil (n=6)
  • Anti-thymocyte globulin was administered to 19 patients
  • Eleven patients also had liver and skin aGvHD
Key findings:
  • The early treatment group received Vd earlier, a median 13 days after steroids starting (range, 5–35) and 24 days (range, 11–351), P = 0.07
  • The early treatment group received more Vd infusions: median 4 (1–12 ) vs 2 (1–4), P = 0.007, respectively
  • Response rates in the early and late treatment groups:
    • ORR (CR+PR) = 11/11 vs 10/16, P = 0.01
    • CR rate = 6/11 vs 3/16, P = 0.04
    • Overall survival rate = 5/11 vs 1/16, P = 0.03, respectively
    • The early treatment group had a higher chance of being off IS: 8/11 vs 3/16, P = 0.004
    • The early treatment group had less fatal infectious complications: 5/11 vs 16/16, P = 0.007

Professor Nagler concluded his talk by stating that “this data suggests that targeting integrin α4β7 may ameliorate severe SR GI aGvHD, especially when Vd is started early, as second line treatment after steroids failure.” He further added that “the role of Vd currently explore in a prospective clinical trial.”

References
  1. Nagler A. et al. Anti α4β7 integrin monoclonal antibody (vedolizumab) for the treatment of steroid-resistant severe intestinal acute graft-versus-host disease. OS12-5. 2018 March 21. 44th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT).
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