Ofatumumab as front-line therapy in untreated chronic lymphocytic leukemia

Ofatumumab is a fully human IgG1 type I anti-CD20 monoclonal antibody that binds to both the small and large loop of the membrane antigen CD20. Much of its therapeutic efficacy is derived through complement-dependent cytotoxicity, although it also appears to operate via induction of caspase-dependent apoptosis and shows potent antibody-dependent cellular phagocytosis. CD20 is an important but sometimes difficult antigen to effectively target in chronic lymphocytic leukemia (CLL) secondary to its overall dim expression in CLL cells. Currently, ofatumumab is approved in the USA and EU for fludarabine- and alemtuzumab-refractory CLL patients. However, the experience with ofatumumab in untreated CLL patients is mounting and shows competitive response and survival rates with an acceptable adverse event profile. Herein, we outline the efficacy and toxicities of ofatumumab alone and in combination for the front-line treatment of CLL.