Ofatumumab is a fully human anti-CD20 monoclonal antibody that induces antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity in CD20-expressing B lymphocytes. Ofatumumab is highly potent in lysing B cells, and this appears to stem from its binding site on the short extracellular loop of the target CD20 protein and its slow release from the target molecule.
In a pivotal, noncomparative study in patients with fludarabine- and alemtuzumab-refractory chronic lymphocytic leukaemia (CLL), ofatumumab induced objective responses in 58% (99% CI 40, 74) of patients, which met a prespecified superiority criterion. The median duration of response was 7.1 months.
The median progression-free survival was 5.7 months and the median overall survival was 13.7 months.
In patients with fludarabine- and alemtuzumab-refractory CLL, infections and neutropenia were the most frequent treatment-related adverse events (all grades) that occurred during ofatumumab treatment; infections that commenced during treatment led to death in five patients (8%).
- 3.Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008 Jun 15; 111(12): 5446–56PubMedCrossRefGoogle Scholar
- 7.GlaxoSmithKline. Arzerra™: prescribing information [online]. Available from URL: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125326lbl.pdf [Accessed 2010 Jan 25]
- 8.Genmab. GlaxoSmithKline receives conditional marketing authorization in the EU for Arzerra™ (ofatumumab) [media release]. 2010 Apr 19Google Scholar
- 11.Pawluczkowycz AW, Beurskens FJ, Beum PV, et al. Binding of submaximal C1q promotes complement-dependent cytotoxicity (CDC) of B cells opsonized with anti-CD20 mAbs ofatumumab (OFA) or rituximab (RTX): considerably higher levels of CDC are induced by OFA than by RTX. J Immunol 2009 Jul 1; 183(1): 749–58PubMedCrossRefGoogle Scholar
- 13.Craigen JL, Mackus WJM, Engleberts P, et al. Ofatumumab, a human Mab targeting a membrane-proximal small-loop epitope on CD20, induces potent NK cell-mediated ADCC [abstract no. 1725]. 51st Annual Meeting and Exposition of the American Society of Hematology; 2009 Dec 5–8; New Orleans (LA)Google Scholar
- 14.GlaxoSmithKline. Arzerra™ (ofatumumab) injection for intravenous use: FDA Oncological Drugs Advisory Committee briefing document [online]. Available from URL: http://www.fda.gov/ohrms/dockets/ac/09/briefing/2009-4444b1-02-GSK.pdf [Accessed 2010 Jan 26]
- 15.Osterborg A, Biilmann Ronn B, Jewell RC, et al. Correlation between serum ofatumumab concentrations, baseline patient characteristics and clinical outcomes in patients with fludarabine-refractory chronic lymphocytic leukemia (CLL) treated with single-agent ofatumumab [abstract no. 3433]. 51st Annual Meeting and Exposition of the American Society of Hematology; 2009 Dec 5–8; New Orleans (LA)Google Scholar
- 18.National Cancer Institute. Common terminology criteria [online]. Available from URL: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf[Accessed2010Feb3]
- 19.European Medicines Agency. Arzerra: summary of opinion (initial authorisation) [online]. Available from URL: http://www.emea.europa.eu/pdfs/human/opinion/Arzerra_214261en.pdf [Accessed 2010 Jan 25]