Jorge Castillo1, Cannon Milani, Daniel Mendez-Allwood. 1. Brown University Warren Alpert Medical School, The Miriam Hospital, Division of Hematology and Oncology, Providence, RI 02906, USA. jcastillo@lifespan.org
Abstract
BACKGROUND: Lymphoproliferative and autoimmune disorders share monoclonal dysregulation and survival advantage of B-lymphocytes. Thus, therapies directed towards eliminating B-cells will play an important role as CD20 is exclusively expressed in B-lymphocytes and its modulation by monoclonal antibodies such as rituximab has improved outcomes in lymphoproliferative and autoimmune disorders. Ofatumumab is a new, fully human anti-CD20 antibody and has been shown to be effective and safe, but its role in these conditions is still unclear. OBJECTIVES: To describe the preclinical and clinical data available on ofatumumab for the treatment of lymphoproliferative and autoimmune disorders. METHODS: An extensive search of published articles and abstracts on preclinical and clinical studies with ofatumumab was undertaken. CONCLUSIONS: Ofatumumab is a second-generation anti-CD20 antibody that has been demonstrated to be safe and efficacious in patients with lymphoproliferative and autoimmune disorders. Ofatumumab is fully human, attaches to a newly identified epitope and shows lower off-rates and improved complement-dependent cytotoxicity. Initial data present ofatumumab as an attractive agent with lower rates of infusion-related events than rituximab. Ongoing Phase III trials in patients with follicular lymphoma, chronic lymphocytic leukemia and rheumatoid arthritis are ongoing, and Phase II trials in patients with aggressive lymphoma and multiple sclerosis are also under development.
BACKGROUND:Lymphoproliferative and autoimmune disorders share monoclonal dysregulation and survival advantage of B-lymphocytes. Thus, therapies directed towards eliminating B-cells will play an important role as CD20 is exclusively expressed in B-lymphocytes and its modulation by monoclonal antibodies such as rituximab has improved outcomes in lymphoproliferative and autoimmune disorders. Ofatumumab is a new, fully human anti-CD20 antibody and has been shown to be effective and safe, but its role in these conditions is still unclear. OBJECTIVES: To describe the preclinical and clinical data available on ofatumumab for the treatment of lymphoproliferative and autoimmune disorders. METHODS: An extensive search of published articles and abstracts on preclinical and clinical studies with ofatumumab was undertaken. CONCLUSIONS:Ofatumumab is a second-generation anti-CD20 antibody that has been demonstrated to be safe and efficacious in patients with lymphoproliferative and autoimmune disorders. Ofatumumab is fully human, attaches to a newly identified epitope and shows lower off-rates and improved complement-dependent cytotoxicity. Initial data present ofatumumab as an attractive agent with lower rates of infusion-related events than rituximab. Ongoing Phase III trials in patients with follicular lymphoma, chronic lymphocytic leukemia and rheumatoid arthritis are ongoing, and Phase II trials in patients with aggressive lymphoma and multiple sclerosis are also under development.
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