The latest developments with anti-CD20 monoclonal antibodies in chronic lymphocytic leukemia

ABSTRACT

Introduction: In more recent years, anti-CD20 monoclonal antibodies have become the backbone in the treatment of chronic lymphocytic leukemia (CLL). Historically, these antibodies were typically combined with chemotherapeutic agents. At present, therapeutic outcomes are significantly improving with the introduction of several novel targeted drugs to the clinical repertoire.

Areas covered: In this review, we summarize the current clinical standard together with the latest developments in the field of anti-CD20 antibodies against CLL. In addition, novel promising drugs against CLL are discussed, as well as their potential for combination with anti-CD20 monoclonal antibodies.

Expert opinion: At present, there are three different anti-CD20 monoclonal antibodies approved for the treatment of CLL with diverse effector mechanisms. These antibodies provide a robust foundation for combination therapy with novel molecules. Current research should be focused on reducing toxicity and reaching long-lasting remissions. There is still much to gain regarding the optimization of treatment combinations and dosing schedules for CLL. Overcoming the limitations of currently used anti-CD20 antibodies will be critical to further improve the efficacy of CLL therapy.

KEYWORDS:

• CD20
• CLL
• antibody
• leukemia
• combination therapy

Article highlights

• Chemoimmunotherapy is still the first-line treatment for the majority of CLL patients. However, for relapsed and refractory patients, and patients in poor prognostic groups, the amount of therapeutic options has recently expanded with the approval of antagonists of B-cell receptor signaling pathways and proapoptotic drugs.

• Albeit there are three anti-CD20 antibodies accepted for the treatment of CLL, novel anti-CD20 antibodies are being investigated for the treatment of CLL.

• A large amount of the ongoing clinical trials for the treatment of CLL are focused on combination therapy with CD20 monoclonal antibodies and inhibitors of B-cell signaling pathways. The majority of trials combines either rituximab or obinutuzumab with other compounds.

• Checkpoint inhibitors, MCL-1 inhibitors, and CAR-T cells are being investigated for treatment of CLL and are showing promising preclinical and clinical results.

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Acknowledgments

We thank Kaylee Keller for critically reading the manuscript for correct English wording and grammar.

Declaration of Interest

M Evers is supported by KWF Kankerbestrijding (R3695). 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.

Reviewer Disclosures

One of the reviewers on this manuscript has consulted for Celgene and Daiichi Sankyo Co., Ltd; received honoraria from Chugai, Kyowa Hakko Kirin, Eisai, Zenyaku Kogyo, Takeda, Celgene, Janssen, HUYA Bioscience, Daiichi Sankyo Co., Ltd, Mundipharma, Ono Pharmaceutical; and received research funding from AbbVie, Chugai, Kyowa Hakko Kirin, Eisai, GSK, Takeda, Celgene, Servier, Janssen, Mundipharma, Ono Pharmaceutical. The two other peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Supplementary Material

Supplementary data for this article can be accessed here.

Additional information

Funding

KWF Kankerbestrijding [R3695].