title: A phase III study of infliximab and corticosteroids for the initial treatment of acute graft-versus-host disease.
abstract: Anti-Tumor Necrosis Factor Alpha (TNF-alpha) therapy with infliximab has shown to be effective for patients with steroid-refractory acute graft-versus-host disease (aGVHD). An open-labeled, phase III trial was conducted to determine if the addition of infliximab to steroids could improve results for patients with newly diagnosed grade II-IV aGVHD. A total of 63 patients were randomized either to 2 mg/kg/day methylprednisolone (MP) or infliximab+ MP. Average age was 47 years (range: 20-70 years); 64% were male. Fifty-three percent and 51% of patients received a matched-sibling and/or bone marrow (BM) graft. Sixty-seven percent had grade II, 33% grade III-IV aGVHD; 62% had skin, 53% gastrointestinal (GI), and 7% had liver involvement. At days 7 and 28, the response rate for infliximab+ MP versus MP was 52% versus 78%, P=.03 and 62% versus 58%, P=.7, respectively. Cumulative incidences of GVHD-related mortality, nonrelapse mortality (NRM), and overall survival (OS) were not significantly different between the 2 groups (GVHD-related mortality: 38% versus 32%, P=.6; NRM: 52% versus 36%, P=.3; OS: 17% and 28%, P=.4 for infliximab+ MP versus MP, respectively). Patients with newly diagnosed aGVHD derive no benefit from the addition of anti-TNF-alpha therapy with infliximab when compared to corticosteroids alone.
authors.affiliation: Sarah Cannon Blood and Marrow Transplantation Program, Tennessee Oncology/Sarah Cannon Research Institute, Nashville, Tennessee, USA. dcouriel@tnonc.com
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Couriel
authors.forename: Rima
authors.initials: R
authors.lastname: Saliba
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
authors.forename: Sergio
authors.initials: S
authors.lastname: Giralt
authors.forename: Borje
authors.initials: B
authors.lastname: Andersson
authors.forename: Issa
authors.initials: I
authors.lastname: Khouri
authors.forename: Chitra
authors.initials: C
authors.lastname: Hosing
authors.forename: Cindy
authors.initials: C
authors.lastname: Ippoliti
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.forename: Amin
authors.initials: A
authors.lastname: Alousi
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D000069285:Infliximab; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000069285:Infliximab; D008775:Methylprednisolone