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.
