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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5486-5495.
Prepublished online as a Blood First Edition Paper on April 4, 2008; DOI 10.1182/blood-2007-10-117671.
 Previous Article | Next Article 
Submitted October 11, 2007
Accepted March 4, 2008
First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase I/II trial
Anton Hagenbeek*, Ole Gadeberg, Peter Johnson, Lars Moller Pedersen, Jan Walewski, Andrzej Hellmann, Brian K Link, Tadeusz Robak, Marek Wojtukiewicz, Michael Pfreundschuh, Michael Kneba, Andreas Engert, Pieter Sonneveld, Mimi Flensburg, Jorgen Petersen, Nedjad Losic, and John Radford
Department of Hematology, University Medical Center Utrecht, Utrecht, Netherlands
Department of Oncology, Vejle Hospital, Vejle, Denmark
Cancer Research UK, Southamton General Hospital, Southamton, United Kingdom
Department of Hematology, Herlev University Hospital, Herlev, Denmark
Cancer Centre, Maria Sklodowska-Curie Memorial Institute, Warsaw, Poland
Depertment of Hematology, Medical University of Gdansk, Gdansk, Poland
College of Medicine, University of Iowa, Iowa City, United States
Department of Hematology, Medical University of Lodz, Lodz, Poland
Department of Medical Oncology, Comprehensive Cancer Center and Medical University, Bialystok, Poland
Department of Internal Medicine I, Saarland University Medical School, Homburg, Germany
Department of Internal Medicine, University of Kiel, Kiel, Germany
Internal Medicine I, University Hospital of Colonge, Colonge, Germany
Department of Hematology, Erasmus Medical Center Rotterdam, Rotterdam, Netherlands
Clinical Development, Genmab A/S, Copenhagen, Denmark
Drug Safety Medical Department, Genmab A/S, Copenhagen, Denmark
Biometrics, Statistical Department, Genmab A/S, Copenhagen, Denmark
Department of Medical Oncology, Christie Hospital and University of Manchester, Manchester, United Kingdom
* Corresponding author; email: a.hagenbeek{at}amc.uva.nl.
Ofatumumab is a unique monoclonal antibody that targets a distinct small loop epitope on the CD20 receptor. Preclinical data show that ofatumumab is active against B-cell lymphoma/chronic lymphocytic leukemia cell-lines with low CD20-antigen density and increased expression of complement inhibitory molecules. In a Phase I/II trial evaluating safety and efficacy of ofatumumab in relapsed or refractory follicular non-Hodgkin lymphoma (FL) grade 1-2, 4 dose groups of 10 patients received 4 weekly infusions of 300, 500, 700, or 1000 mg. Patients had a median of 2 prior FL therapies and 13% had elevated LDH. No safety concerns or maximum tolerated dose was identified. 274 AEs were reported; 190 were judged related to ofatumumab; most occurring on the first infusion day with CTC grade 1-2. Eight related events were grade 3. Treatment caused immediate and profound B-cell depletion and 65% of patients reverted to negative Bcl-2 status. Clinical response rates ranged from 20-63%. Median time to progression (TTP) for all patients/responders were 8.8/32.6 months and median duration of response was 29.9 months at a median/maximum follow-up of 9.2/38.6 months. Ofatumumab is currently being evaluated in patients with rituximab-refractory FL. This trial was registered at www.clinicaltrials.gov; NCT00092274.
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