Drug Evaluation

Lady Davis Institute, Jewish General Hospital, McGill University, 3755 Cote Ste Catherine, E725, Montreal, QC, H3T 1E2, Canada

*Author for correspondence: Tel.: +1 514 340 8222;

E-mail Address: Sarit.assouline@mcgill.ca

Lady Davis Institute, Jewish General Hospital, McGill University, 3755 Cote Ste Catherine, E725, Montreal, QC, H3T 1E2, Canada

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Published Online:26 Oct 2023https://doi.org/10.2217/fon-2023-0274

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Abstract

Follicular lymphoma (FL) is the most common indolent lymphoma. Since the advent of rituximab, FL has seen a progressive improvement in patient prognosis. While chemotherapy combined with an anti-CD20 monoclonal antibody remains standard first-line therapy, most patients will relapse and require subsequent therapy. T-cell-redirecting therapies can be very potent and are transforming the therapeutic landscape in the relapsed and refractory (R/R) setting. T-cell-dependent bispecific antibodies, of which mosunetuzumab is the first to be approved for R/R FL, are proving to be a highly effective, ‘off-the-shelf’ option with manageable toxicities. This review covers approved treatments for R/R FL and focuses on preclinical and clinical data available for mosunetuzumab (Lunsumio™), with the goal of determining its role in the treatment of R/R FL.

Plain language summary – Novel immune therapy expands treatment options for patients with follicular lymphoma

Follicular lymphoma (FL) is a common and often slowly progressing cancer of B cells, a component of the immune system. While FL is not considered curable, patients’ survival has improved significantly over the last 15 years owing to the addition of new treatments like rituximab (an immunotherapy) and bendamustine (a chemotherapy drug) to the list of available therapies. However, FL patients often experience disease recurrences and need several courses of therapy during their lifetime. In the last 10 years the understanding of how T cells – a key part of the body’s natural defense against disease – can help kill cancerous cells has grown tremendously, leading to the development of highly effective treatments that harness these T cells to kill cancer cells. Mosunetuzumab, one such therapy, is an antibody that can bind both the T cells and the cancerous B cells of FL. Bringing the T cell to the cancerous B cell causes T-cell activation and killing of the lymphoma. It has proven highly effective, and mosunetuzumab has recently been approved in Europe and the USA for the treatment of recurrent FL. This review focuses on the design and testing of mosunetuzumab in the laboratory and in patients, and explains its mode of action and potential role in the treatment of relapsed/refractory FL.

Tweetable abstract

Mosunetuzumab is the first T-cell-dependent bispecific antibody to receive regulatory approval for R/R follicular lymphoma. This review describes the therapeutic landscape of follicular lymphoma and the preclinical and clinical data for mosunetuzumab.

Keywords:

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

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Vol. 19, No. 31

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History

Received 31 March 2023

Accepted 22 September 2023

Published online 26 October 2023

Published in print October 2023

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Financial disclosure

S Matarasso: none. S Assouline declares honoraria for advisory boards: AstraZeneca, BMS, Gilead, Roche Genentech, Abbvie, Novartis, Janssen and research support from Novartis. 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.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

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

Company review disclosure

In addition to the peer-review process, with the authors’ 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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Mosunetuzumab and the emerging role of T-cell-engaging therapy in follicular lymphoma

Abstract

Plain language summary – Novel immune therapy expands treatment options for patients with follicular lymphoma

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References