Ofatumumab for the treatment of chronic lymphocytic leukemia

Author(s): Tadeusz Robak

Over the last few years, several new monoclonal antibodies (mAbs) directed against lymphoid cells have been developed and investigated in chronic lymphocytic leukemia (CLL). Two mAbs have been demonstrated to have the most important clinical value in patients with CLL – rituximab, which targets the CD20 antigen, and alemtuzumab, which is active against the CD52 antigen. Recently, several new mAbs have been explored and evaluated in preclinical studies and in early clinical trials. One of these is ofatumumab (HuMax-CD20™), a fully human monoclonal immunoglobulin (Ig)G1-k antibody targeting a CD20 molecule on B cells. Ofatumumab specifically recognizes an epitope encompassing both the small and large extracellular loops of CD20, distinct from the epitope recognized by rituximab. Ofatumumab, in comparison with rituximab, shows superiority in complement-dependent cytotoxicity of B cells, and does not induce cell death of tumor B cells by apoptosis. In a Phase I/II study, ofatumumab demonstrated significant depletion of CD19+/CD5+ CLL cells, and showed a favorable safety profile in previously treated CLL patients. A recent study demonstrates the effectiveness of ofatumumab in patients with fludarabine-refractory CLL. Ofatumumab potentially represents an active treatment option with clinical benefit for patients with very poor prognosis who have exhausted standard treatment options. In December 2004, the US FDA granted Fast Track status for the use of ofatumumab in therapy of CLL in patients who failed treatment with fludarabine.