Anti-CD20 Antibodies for Chronic Lymphocytic Leukemia

There are 3 anti-CD20 antibodies that have been approved for the treatment of patients with chronic lymphocytic leukemia (CLL): rituximab, ofatumumab, and obinutuzumab. These agents work through several mechanisms of action, including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and direct induction of apoptosis. These monoclonal antibodies have shown significant improvements in overall survival for patients with CLL and are most effective when used in combination with chemotherapy, states William Wierda, MD, PhD.

Rituximab was the first anti-CD20 antibody and works through ADCC and CDC. Ofatumumab, the second antibody approved for CLL, binds to a different site on CD20 than rituximab and possesses higher levels of CDC activity. It also works via ADCC. Rituximab and ofatumumab are considered type 1 antibodies, comments Wierda.

Obinutuzumab is a type 2 monoclonal antibody that functions predominantly through direct induction of apoptosis, with lower effectiveness via ADCC and CDC. However, it has been glycoengineered to increase ADCC effectiveness over that of the original antibodies, says Wierda.

Analyses assessing the costs of chemo-immunotherapy versus chemo-immunotherapy followed by a small molecule inhibitor demonstrated remarkably increased cost with the addition of a small molecule inhibitor. Patients receiving chemo-immunotherapy and a small molecule inhibitor live longer, and the number of patients on these agents will increase, says Wierda. It is important to address costs so that patients are not prohibited from receiving effective therapies that will prolong survival, notes Wierda.