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Obinutuzumab in chronic lymphocytic leukemia: design, development and place in therapy

Authors Al-Sawaf O, Fischer K, Engelke A, Pflug N, Hallek M, Goede V

Received 6 October 2016

Accepted for publication 7 December 2016

Published 25 January 2017 Volume 2017:11 Pages 295—304

DOI https://doi.org/10.2147/DDDT.S104869

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Dr James Janetka

Othman Al-Sawaf, Kirsten Fischer, Anja Engelke, Natali Pflug, Michael Hallek, Valentin Goede

German CLL Study Group, Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany

Abstract: For decades, treatment of chronic lymphocytic leukemia (CLL) has been based on chemotherapy. This changed when the first CD20 antibody rituximab was introduced. Since 2008, the combination of chemotherapy and CD20 antibodies has become the standard of care for most patients, and a significant fraction of patients had very long-lasting remissions after chemoimmunotherapy. Despite the improvement of response rates and overall survival (OS) by the use of chemoimmunotherapy, most CLL patients will relapse eventually. One approach to achieve more durable responses was the development of obinutuzumab (GA101), a new type of CD20 antibody that has unique molecular and functional characteristics. Obinutuzumab is a type II fully humanized CD20 antibody that binds to a partly different epitope of the CD20 protein than rituximab and due to its glycoengineered design induces greater antibody-dependent cell-mediated cytotoxicity (ADCC). Initial preclinical observations of a more effective B-cell depletion have been successfully reproduced in clinical trials with CLL patients. This review summarizes results of preclinical as well as clinical studies with obinutuzumab and provides an outlook on its future role in the therapy of CLL.

Keywords: chronic lymphocytic leukemia, GA101, obinutuzumab, CD20 antibody

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