Ofatumumab (Arzerra) is a human IgG1k monoclonal antibody directed to the B-cell surface antigen CD20. Ofatumumab binds to both the small and large extracellular loops of the CD20 molecule, which is an epitope specificity different from that of rituximab and most other CD20 directed antibodies. It appears to promote more effective complement deposition and ADCC.
The recommended dose and schedule for ofatumumab is 300 mg by iv infusion on day 1 followed by 1000 mg on day 8 and then 7 weeks thereafter for up to a maximum of 2 years.
Ofatumumab received accelerated approval from the FDA in 2009 for treating chronic lymphocytic leukemia (CLL) that is refractory to fludarabine and alemtuzumab and received regular approval in April 2014 for its use in combination with chlorambucil, for previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate. In 2015, FDA granted a priority review designation to ofatumumab as a maintenance therapy for relapsed CLL. In January 2016, FDA approved ofatumumab for extended treatment of patients who are in complete or partial response after at least two lines of therapy for the treatment of previously untreated patients with CLL.
Its use in other conditions treated by rituximab is not yet established, but clinical trials are completed or underway for its use in follicular lymphoma, relapsed/refractory DLBCL, Non-Hodgkin’s Lymphoma, Acute lymphocytic leukemia, chronic graft-versus-host disease, Waldenstrom’s Macroglobulinemia, Pemphigus Vulgaris, and Multiple Sclerosis.
The major safety concerns are infusion reactions, cytopenias, hepatitis B, and progressive multifocal leukoencephalopathy (PML), neutropenia, asthenia, headache, leukopenia, herpes simplex viral infection, lower respiratory tract infection, joint pain, and upper abdominal pain.
Human IgG1k monoclonal antibody, recombinant
Chronic lymphocytic leukemia resistant to fludarabine and alemtuzumab
Glaxo Smith Kline, Novartis
Initial FDA Approval
Package Insert: http://us.gsk.com/products/assets/us_arzerra.pdfâ€¨â€¨
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