Combination therapy with the type II anti-CD20 antibody obinutuzumab

ABSTRACT

Introduction: Obinutuzumab is a novel humanized type II glycoengineered anti-CD20 antibody approved for first-line treatment of chronic lymphocytic leukemia (CLL) in combination with chlorambucil and for treatment of rituximab-refractory follicular lymphoma (FL).

Areas covered: We describe current preclinical and clinical evidence supporting the combination of obinutuzumab with not only chemotherapy but also novel targeted therapies for B-cell hematologic malignancies, and its application in chemoimmunotherapy. We also provide an overview of the current clinical trial landscape investigating novel combination therapies based on obinutuzumab.

Expert opinion: Within the next 10 years the treatment of B-cell malignancies with obinutuzumab is expected to increasingly move towards chemotherapy-free regimens. Novel combinations of obinutuzumab will be explored with targeted therapies, antibody–drug conjugates, and/or other immunotherapeutic agents, with the aim to achieve clinically meaningful improvements in efficacy and patient safety.

KEYWORDS:

• B-cell lymphoma
• CD20
• chronic lymphocytic leukemia
• non-Hodgkin lymphoma
• obinutuzumab
• targeted therapy

Article highlights

• Obinutuzumab is a first-in-class humanized type II glycoengineered anti-CD20 antibody developed for use against various types of B-cell malignancies and currently approved for first-line treatment of chronic lymphocytic leukemia (CLL) in combination with chlorambucil and for treatment of rituximab-refractory follicular lymphoma (FL) in combination with bendamustine.

• Obinutuzumab exerts more potent direct cell killing and antibody-dependent cell-mediated cytotoxicity (ADCC) compared with rituximab in B-cell malignancies. These advantages are being explored for combinations of obinutuzumab with pro-apoptotic factors, kinase inhibitors, monoclonal antibody–drug conjugates, and immunomodulators.

• Options not yet in clinical development but that hold potential include other B-cell ligand targets, agents against immunosuppressive mechanisms that can limit anti-CD20 efficacy, immunocytokines, and adoptive immunotherapy approaches such as chimeric antigen receptors and cytokine-induced killer cells.

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Declaration of interest

Third party medical writing support was provided by Gardiner-Caldwell Communications Ltd, funded by F. Hoffmann-La Roche Ltd. All authors are employees of and own stocks of F. Hoffmann-La Roche Ltd. 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.

Additional information

Funding

This paper was funded by F. Hoffmann-La Roche Ltd.