A phase 3 randomized trial comparing inolimomab vs usual care in steroid-resistant acute GVHD

  • Blood. 2017 Feb 2;129(5):643-649. doi: 10.1182/blood-2016-09-738625.
Gérard Socié  1  2  3 ,  Stéphane Vigouroux  4 ,  Ibrahim Yakoub-Agha  5 ,  Jacques-Olivier Bay  6 ,  Sabine Fürst  7 ,  Karin Bilger  8 ,  Felipe Suarez  9 ,  Mauricette Michallet  10 ,  Dominique Bron  11 ,  Philippe Gard  12 ,  Zakaria Medeghri  12 ,  Philippe Lehert  13 ,  Chinglin Lai  14 ,  Tim Corn  15 ,  Jean-Paul Vernant  16
Affiliations
  • 1. Service d'Hématologie-Greffe, Assistance Publique-Hôpitaux de Paris, Hôpital St-Louis Lariboisière, Paris, France.
  • 2. Department of Medicine, Université Paris 7 Denis Diderot, Paris, France.
  • 3. INSERM UMR 1160, Paris, France.
  • 4. Service d'hématologie clinique et thérapie cellulaire, Hôpital Haut-Lévêque, Pessac, France.
  • 5. CHU de Lille, LIRIC INSERM U995, Université Lille2, Lille, France.
  • 6. Service thérapie cellulaire et hématologie clinique, CHU, Clermont-Ferrand, France.
  • 7. Unité de Transplantation et de Thérapie Cellulaire, Institut Paoli Calmettes, Marseille, France.
  • 8. Service d'Onco-Hématologie, CHU Hautepierre, Strasbourg, France.
  • 9. Service d'hématologie adulte, Hôpital Necker, Paris, France.
  • 10. Service d'hématologie, Hôpital Lyon Sud, Lyon, France.
  • 11. Service d'hématologie, Institut Jules Bordet (ULB), Bruxelles, Belgium.
  • 12. EUSA Pharma (Europe) Limited (a Jazz Pharmaceuticals company), Lyon, France.
  • 13. Faculty of Medicine, University of Melbourne, Melbourne, VIC, Australia.
  • 14. Jazz Pharmaceuticals, Palo Alto, CA.
  • 15. Jazz Pharmaceuticals, Oxford, United Kingdom; and.
  • 16. Service d'hématologie clinique, Hôpital Pitié Salpêtrière, Paris, France.
PMID: 27899357 DOI: 10.1182/blood-2016-09-738625
Abstract

Treatment of steroid-resistant acute graft-versus-host disease (GVHD) remains an unmet clinical need. Inolimomab, a monoclonal antibody to CD25, has shown encouraging results in phase 2 trials. This phase 3 randomized, open-label, multicenter trial compared inolimomab vs usual care in adult patients with steroid-refractory acute GVHD. Patients were randomly selected to receive treatment with inolimomab or usual care (the control group was treated with antithymocyte globulin [ATG]). The primary objective was to evaluate overall survival at 1 year without changing baseline allocated therapy. A total of 100 patients were randomly placed: 49 patients in the inolimomab arm and 51 patients in the ATG arm. The primary criteria were reached by 14 patients (28.5%) in the inolimomab and 11 patients (21.5%) in the ATG arms, with a hazard ratio of 0.874 (P = .28). With a minimum follow-up of 1 year, 26 (53%) and 31 (60%) patients died in the inolimomab and ATG arms, respectively. Adverse events were similar in the 2 arms, with fewer viral infections in the inolimomab arm compared with the ATG arm. The primary end point of this randomized phase 3 trial was not achieved. The lack of a statistically significant effect confirms the need for development of more effective treatments for acute GVHD. This trial is registered to https://www.clinicaltrialsregister.eu/ctr-search/search as EUDRACT 2007-005009-24.

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