Mosunetuzumab treats certain cancers, particularly those affecting the lymphatic system, by engaging the body’s own immune system to combat malignant cells. It offers options for patients who have limited choices after previous treatments.
Understanding Mosunetuzumab
Mosunetuzumab is a bispecific T-cell engaging antibody engineered to bind to two distinct targets. One arm of the antibody recognizes CD20, a protein found on the surface of B-cells, including cancerous B-cells in lymphomas such as follicular lymphoma. The other arm targets CD3, a component of the T-cell receptor complex present on T-cells, which are immune cells capable of destroying other cells.
This dual binding action brings the patient’s own T-cells into close proximity with the malignant B-cells. Once this connection is established, the T-cells become activated and release cytotoxic substances like perforin and granzymes directly onto the cancer cells. This targeted mechanism leads to the destruction of the malignant B-cells, bypassing some of the resistance mechanisms that can develop with other therapies.
The FDA Approval and Its Significance
The U.S. Food and Drug Administration (FDA) granted accelerated approval to mosunetuzumab-axgb (brand name Lunsumio) on December 22, 2022. This approval targets adult patients with relapsed or refractory follicular lymphoma (FL) who have undergone at least two prior lines of systemic therapy, including an anti-CD20 monoclonal antibody and an alkylating agent. Follicular lymphoma is a slow-growing form of non-Hodgkin lymphoma, and patients with relapsed or refractory disease often face limited treatment options.
The accelerated approval was based on the GO29781 study, an open-label, multicenter, multi-cohort trial. In this study, 80% of patients achieved an objective response rate, with 60% experiencing a complete response. The median duration of response for those who responded was an estimated 22.8 months, with response rates at 12 and 18 months being 62% and 57% respectively.
Mosunetuzumab is the first CD20xCD3 T-cell engaging bispecific antibody approved by the FDA, offering a new, non-chemotherapy treatment option for this specific patient population. It addresses an unmet medical need for individuals whose cancer has returned or has not responded to previous treatments.
Patient Considerations and Side Effects
Patients receiving mosunetuzumab are given the drug as an intravenous infusion. The typical treatment schedule involves a step-up dosing approach in the first cycle, with smaller doses on Day 1 and Day 8, followed by a higher dose on Day 15. This step-up dosing is designed to help reduce the risk of certain side effects.
The most commonly reported side effects, occurring in 20% or more of patients, include cytokine release syndrome (CRS), fatigue, rash, fever, and headache. Cytokine release syndrome can be serious or life-threatening and may involve symptoms such as fever, chills, low blood pressure, fast heartbeat, or difficulty breathing. Neurological toxicities, including confusion, dizziness, or problems with balance, have also been observed in a notable percentage of patients.
Serious infections, such as pneumonia or sepsis, have been reported in patients treated with mosunetuzumab, with some cases being fatal. Patients should be monitored for signs of infection before and during treatment. Healthcare providers will closely monitor patients for these and other potential side effects, and patients are advised to discuss any concerns or new symptoms with their care team immediately.