title: Ofatumumab in combination with glucocorticoids for primary therapy of chronic graft-versus-host disease: phase I trial results.
abstract: Standard primary therapy for chronic graft-versus-host disease (GVHD) is incompletely effective. Based on biologic insights implicating pathogenic B cells, we conducted a phase I trial examining the combination of standard (1 mg/kg/day prednisone) glucocorticoid therapy with ofatumumab, a humanized anti-CD20 monoclonal antibody, for primary chronic GVHD therapy. Patients ages ≥ 18 with National Institutes of Health Consensus moderate-to-severe chronic GVHD newly requiring 1 mg/kg/day prednisone were treated at 3 escalating dose levels (300 mg, 700 mg, and 1000 mg) of i.v. ofatumumab on days 1 and 14 of initial glucocorticoid therapy. Dose-limiting toxicity (DLT) was defined by grade 4 infusion reactions, related grade 4 constitutional symptoms, related grade ≥ 3 organ toxicities, or grade 4 neutropenia lasting > 14 days. A total of 12 patients (median age 54; range, 25 to 72) were treated (dose level 1: n = 3; level 2: n = 3; level 3: n = 6). At enrollment, overall chronic GVHD was moderate (n = 7) or severe (n = 5), with diverse organ involvement (skin: n = 8; mouth: n = 8; eye: n = 8; lung: n = 4; gastrointestinal: n = 3; liver: n = 5; genital: n = 2; joint/fascia: n = 5). Infusion of ofatumumab was well tolerated, and no DLT was observed. From the total number of adverse events (n = 29), possibly related adverse events (n = 4) included grade 1 fatigue, grade 1 transaminitis, and 2 infusion reactions (grades 2 and 3). Infectious complications were expected, and there were no cases of hepatitis B reactivation or progressive multifocal leukoencephalopathy. Ofatumumab in combination with prednisone is safe and a phase II examination of efficacy is ongoing.
authors: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida; Oncologic Sciences, College of Medicine at University of South Florida, Tampa, Florida. Electronic address: joseph.pidala@moffitt.org.
authors: Joseph
authors: J
authors: Pidala
authors: Oncologic Sciences, College of Medicine at University of South Florida, Tampa, Florida; Biostatistics, Moffitt Cancer Center, Tampa, Florida.
authors: Jongphil
authors: J
authors: Kim
authors: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida; Oncologic Sciences, College of Medicine at University of South Florida, Tampa, Florida.
authors: Brian C
authors: BC
authors: Betts
authors: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida; Oncologic Sciences, College of Medicine at University of South Florida, Tampa, Florida.
authors: Melissa
authors: M
authors: Alsina
authors: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida; Oncologic Sciences, College of Medicine at University of South Florida, Tampa, Florida.
authors: Ernesto
authors: E
authors: Ayala
authors: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida; Oncologic Sciences, College of Medicine at University of South Florida, Tampa, Florida.
authors: Hugo F
authors: HF
authors: Fernandez
authors: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida; Oncologic Sciences, College of Medicine at University of South Florida, Tampa, Florida.
authors: Teresa
authors: T
authors: Field
authors: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida; Oncologic Sciences, College of Medicine at University of South Florida, Tampa, Florida.
authors: Mohamed A
authors: MA
authors: Kharfan-Dabaja
authors: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida; Oncologic Sciences, College of Medicine at University of South Florida, Tampa, Florida.
authors: Frederick L
authors: FL
authors: Locke
authors: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida; Oncologic Sciences, College of Medicine at University of South Florida, Tampa, Florida.
authors: Asmita
authors: A
authors: Mishra
authors: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida; Oncologic Sciences, College of Medicine at University of South Florida, Tampa, Florida.
authors: Taiga
authors: T
authors: Nishihori
authors: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida; Oncologic Sciences, College of Medicine at University of South Florida, Tampa, Florida.
authors: Leonel
authors: L
authors: Ochoa-Bayona
authors: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida; Oncologic Sciences, College of Medicine at University of South Florida, Tampa, Florida.
authors: Lia
authors: L
authors: Perez
authors: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida; Oncologic Sciences, College of Medicine at University of South Florida, Tampa, Florida.
authors: Marcie
authors: M
authors: Riches
authors: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida; Oncologic Sciences, College of Medicine at University of South Florida, Tampa, Florida.
authors: Claudio
authors: C
authors: Anasetti
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use*; D035781:Siblings; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C527517:ofatumumab; D011241:Prednisone
keywords: Chronic graft-versus-host disease; Ofatumumab; Prednisone; Primary therapy