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Rituximab, Obinutuzumab, and Ofatumumab in CLL

Panelists: Ivan Marques Borello, MD, Johns Hopkins; Myron S. Czuczman, MD, Roswell Park; Madhav V. Dhodapkar, MBBS, Yale; Dan Douer, MD, MSK 
Published: Monday, Jun 29, 2015

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At this point, there are 3 anti-CD20 monoclonal antibodies approved as treatments for patients with chronic lymphocytic leukemia (CLL): rituximab (Rituxan), obinutuzumab (Gazyva), and ofatumumab (Arzerra), states Myron Czuczman, MD. Although they all target CD20, these 3 agents have different mechanisms of action, different structures, and functions.
 
Rituximab is a class I chimeric anti-CD20 antibody that induces both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), and may also be involved in direct signaling. Obinutuzumab, also known as GA101, is a class II CD20 antibody. It is more effective than rituximab at eliciting ADCC but has very little impact on CDC. Ofatumumab is a fully human monoclonal antibody that was designed to have superior CDC to rituximab. The treatment also possesses ADCC activity. 

Obinutuzumab was designed to work when effector cells are more intact, says Czuczman. For example, individuals with end-stage disease who have received 3 to 4 cycles of different therapies may not have as robust of an immune system or complete effector cells as newly diagnosed, untreated individuals. In contrast to obinutuzumab, which was designed to work with effector cells, ofatumumab was meant to target complement cells, which may not be as depleted in patients with end-stage disease who have received many lines of therapy. This mechanism makes ofatumumab preferred in the later course of therapy, notes Czuczman.
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For High-Definition, Click
At this point, there are 3 anti-CD20 monoclonal antibodies approved as treatments for patients with chronic lymphocytic leukemia (CLL): rituximab (Rituxan), obinutuzumab (Gazyva), and ofatumumab (Arzerra), states Myron Czuczman, MD. Although they all target CD20, these 3 agents have different mechanisms of action, different structures, and functions.
 
Rituximab is a class I chimeric anti-CD20 antibody that induces both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), and may also be involved in direct signaling. Obinutuzumab, also known as GA101, is a class II CD20 antibody. It is more effective than rituximab at eliciting ADCC but has very little impact on CDC. Ofatumumab is a fully human monoclonal antibody that was designed to have superior CDC to rituximab. The treatment also possesses ADCC activity. 

Obinutuzumab was designed to work when effector cells are more intact, says Czuczman. For example, individuals with end-stage disease who have received 3 to 4 cycles of different therapies may not have as robust of an immune system or complete effector cells as newly diagnosed, untreated individuals. In contrast to obinutuzumab, which was designed to work with effector cells, ofatumumab was meant to target complement cells, which may not be as depleted in patients with end-stage disease who have received many lines of therapy. This mechanism makes ofatumumab preferred in the later course of therapy, notes Czuczman.
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