Ofatumumab in Combination with Glucocorticoids for Primary Therapy of Chronic Graft-versus-Host Disease: Phase I Trial Results

Joseph Pidala, Jongphil Kim, Brian C. Betts, Melissa Alsina, Ernesto Ayala, Hugo F. Fernandez, Teresa Field, Mohamed A. Kharfan-Dabaja, Frederick L. Locke, Asmita Mishra, Taiga Nishihori, Leonel Ochoa-Bayona, Lia Perez, Marcie Riches, Claudio Anasetti

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1074-1082
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume21
Issue number6
DOIs
StatePublished - Jun 2015
Externally publishedYes

Bibliographical note

Funding Information:
Financial disclosure: This investigator-initiated trial was conducted with support from GlaxoSmithKline . The principal investigator's effort was also in part supported by the American Cancer Society ( MRSG-11-149-01-LIB , PI: J.P). This work has been supported in part by the Biostatistics Core Facility at the H. Lee Moffitt Cancer Center & Research Institute, a National Cancer Institute –designated Comprehensive Cancer Center ( P30-CA076292 ).

Publisher Copyright:
© 2015 American Society for Blood and Marrow Transplantation.

Keywords

  • Chronic graft-versus-host disease
  • Ofatumumab
  • Prednisone
  • Primary therapy

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