Ofatumumab

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Ofatumumab

Ofatumumab is a monoclonal antibody specifically designed for the treatment of B cell chronic lymphocytic leukemia (CLL). It is a fully human monoclonal antibody that targets an epitope on the CD20 molecule encompassing parts of the small and large extracellular loops.

Mechanism of Action

Ofatumumab binds to the CD20 molecule on B cells, leading to immune-mediated B cell lysis. The CD20 molecule is expressed on more than 90% of B cell CLL. The binding of the antibody to the CD20 molecules induces antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), leading to the lysis of the target cells.

Clinical Use

Ofatumumab is used for the treatment of patients with CLL refractory to fludarabine and alemtuzumab. It is also used in combination with chlorambucil or bendamustine for the treatment of patients with untreated CLL who are not candidates for fludarabine-based therapy.

Side Effects

The most common side effects of ofatumumab include neutropenia, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, dyspnea, rash, nausea, bronchitis, and upper respiratory tract infection. Serious side effects include hepatitis B reactivation, progressive multifocal leukoencephalopathy, tumor lysis syndrome, and cytokine release syndrome.

Pharmacokinetics

Ofatumumab is administered intravenously. The pharmacokinetics of ofatumumab have been studied in patients with CLL and follicular lymphoma. The clearance of ofatumumab decreases with increasing doses, and the volume of distribution is approximately equal to the blood volume.

History

Ofatumumab was developed by Genmab and is marketed under the trade name Arzerra. It was approved by the Food and Drug Administration (FDA) in 2009 for the treatment of CLL.

See Also

• Monoclonal antibodies
• Chronic lymphocytic leukemia
• CD20
• Antibody-dependent cellular cytotoxicity
• Complement-dependent cytotoxicity