title: A phase 3 randomized trial comparing inolimomab vs usual care in steroid-resistant acute GVHD.
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.
authors.affiliation: Service d'Hématologie-Greffe, Assistance Publique-Hôpitaux de Paris, Hôpital St-Louis Lariboisière, Paris, France.|Department of Medicine, Université Paris 7 Denis Diderot, Paris, France.|INSERM UMR 1160, Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.affiliation: Service d'hématologie clinique et thérapie cellulaire, Hôpital Haut-Lévêque, Pessac, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Vigouroux
authors.affiliation: CHU de Lille, LIRIC INSERM U995, Université Lille2, Lille, France.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yakoub-Agha
authors.affiliation: Service thérapie cellulaire et hématologie clinique, CHU, Clermont-Ferrand, France.
authors.forename: Jacques-Olivier
authors.initials: JO
authors.lastname: Bay
authors.affiliation: Unité de Transplantation et de Thérapie Cellulaire, Institut Paoli Calmettes, Marseille, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Fürst
authors.affiliation: Service d'Onco-Hématologie, CHU Hautepierre, Strasbourg, France.
authors.forename: Karin
authors.initials: K
authors.lastname: Bilger
authors.affiliation: Service d'hématologie adulte, Hôpital Necker, Paris, France.
authors.forename: Felipe
authors.initials: F
authors.lastname: Suarez
authors.affiliation: Service d'hématologie, Hôpital Lyon Sud, Lyon, France.
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.affiliation: Service d'hématologie, Institut Jules Bordet (ULB), Bruxelles, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bron
authors.affiliation: EUSA Pharma (Europe) Limited (a Jazz Pharmaceuticals company), Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gard
authors.affiliation: EUSA Pharma (Europe) Limited (a Jazz Pharmaceuticals company), Lyon, France.
authors.forename: Zakaria
authors.initials: Z
authors.lastname: Medeghri
authors.affiliation: Faculty of Medicine, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lehert
authors.affiliation: Jazz Pharmaceuticals, Palo Alto, CA.
authors.forename: Chinglin
authors.initials: C
authors.lastname: Lai
authors.affiliation: Jazz Pharmaceuticals, Oxford, United Kingdom; and.
authors.forename: Tim
authors.initials: T
authors.lastname: Corn
authors.affiliation: Service d'hématologie clinique, Hôpital Pitié Salpêtrière, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vernant
mesh_terms: D000208:Acute Disease; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D013256:Steroids / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D013256:Steroids; C079843:inolimomab