ofatumumab

Description

Considered as the most common form of leukemia in adults, CLL is characterized by the accumulation of abnormal B lymphocytes and manifests itself as lymph node enlargement and bone marrow failure in symptomatic patients. Ofatumumab is the second marketed mAb to target CD20. Compared to its predecessor,it is a fully human mAb that was generated via transgenic mouse and hybridoma technology. In addition to the Fab portion that recognizes CD20, the Fc domain mediates immune effector functions to lyse cells via complement-dependent cytotoxicity (CDC) and antibody-dependent, cell-mediated cytotoxicity (ADCC). Ofatumumab targets a different, discontinuous epitope on CD20 than rituximab; it binds specifically to both the small and large extracellular loops of the CD20 molecule expressed on normal B lymphocytes and on B-cell CL, and its binding does not induce receptor internalization nor shedding from the cell surface. In addition to targeting a different epitope on CD20, ofatumumab also exhibits a slower off-rate. These characteristics have been proposed as reasons for its ability to lyse rituximab-resistant cells that express low levels of CD20 and for its greater in vitro activity against CLL cells versus rituximab.
The most common adverse events were neutropenia, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, dyspnea, rash, nausea, bronchitis, and upper respiratory tract infections.

Originator

Genmab (Denmark)

brand name

Arzerra

Clinical Use

IgG1 monoclonal antibody:
Treatment of chronic lymphocytic leukaemia

Drug interactions

Potentially hazardous interactions with other drugs
Live vaccines: avoid concomitant use.

Metabolism

Ofatumumab is eliminated by proteolytic enzymes and via binding to B-cells.