Drug Evaluation

*Author for correspondence:

E-mail Address: ross.salvaris@monashhealth.org

Department of Haematology, Monash Health, 246 Clayton Rd, Clayton, Victoria 3168, Australia; School of Clinical Sciences at Monash Health, Monash University, Wellington Rd, Clayton, Victoria 3800, Australia

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Stephen Opat

https://orcid.org/0000-0002-0308-6458

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Published Online:16 Oct 2020https://doi.org/10.2217/fon-2020-0640

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Abstract

In the last decade, the treatment of chronic lymphocytic leukemia (CLL) has shifted away from chemoimmunotherapy toward targeted novel agents such as small molecule inhibitors and antibodies. Here, we give an overview of the pharmacology of venetoclax and obinutuzumab and the evidence from early phase to Phase III trials that have shaped how they are used in the treatment of CLL. Venetoclax, an oral anti-apoptotic BCL-2 inhibitor, in combination with a CD20 antibody has shown superiority to chemoimmunotherapy in treatment-naive and relapsed/refractory CLL. Obinutuzumab is a novel anti-CD20 monoclonal antibody that has been safely combined with novel agents including venetoclax and Bruton tyrosine kinase inhibitors and has shown superiority over rituximab when combined with chlorambucil.

Lay abstract

In the last decade, the treatment of chronic lymphocytic leukemia (CLL) has shifted away from using chemotherapy agents toward newer drugs including some that may be taken orally. Here, we give an overview of two of these new drugs: obinutuzumab, a newer version of rituximab; and the orally administered venetoclax. Venetoclax, an oral agent that promotes cell death in CLL cells, has been shown to be superior to traditional chemotherapy agents when used in combination with obinutuzumab or rituximab in newly diagnosed or relapsed CLL patients. Obinutuzumab is an antibody, given as an infusion, which targets a protein on the surface of CLL cells called CD20 and has been combined effectively with venetoclax.

Keywords:

Papers of special note have been highlighted as: • of interest

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Vol. 17, No. 4

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History

Received 22 June 2020

Accepted 10 September 2020

Published online 16 October 2020

Published in print February 2021

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Financial & competing interests disclosure

R Salvaris receives an Honoraria from Roche. S Opat receives advisory, Speakers fees, Honoraria from Janssen and Research funding, Advisory, Speakers fees, Honoraria from Roche and Gilead. S Opat receives Research funding from Beigene, Amgen and Advisory fees from Mundipharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Company review disclosure

In addition to the peer-review process, with the author's consent, the manufacturer of the product discussed in this article was given the opportunity to review the manuscript for factual accuracy. Changes were made by the author at their discretion and based on scientific or editorial merit only. The author maintained full control over the manuscript, including content, wording and conclusions.

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An update of venetoclax and obinutuzumab in chronic lymphocytic leukemia

Abstract

Lay abstract

References