Mosunetuzumab and the emerging role of T-cell-engaging therapy in follicular lymphoma.

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. 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.