New bispecific antibody (mosunetuzumab) for the treatment of untreated follicular lymphoma (FL): Comparison with standard therapy

Follicular lymphoma (FL) is a type of non-Hodgkin lymphoma (NHL) in which malignant B lymphocytes accumulate in the lymph nodes. Lymphocytes are a type of white blood cell that is part of the immune system. The cause of FL is not fully understood, but genetic mutations and immune system disorders play a role. This disease is chronic and generally incurable with available standard therapies, but it can often be effectively controlled for a long time. Treatment is tailored to the symptoms and overall health of the affected patients. Patients with early-stage (limited) FL usually receive radiation therapy. Standard treatment for advanced-stage FL often involves a combination of chemotherapy and immunotherapy. In cases of disease recurrence or when FL does not respond to treatment (refractory), a new treatment option is the administration of mosunetuzumab. Mosunetuzumab is an antibody that attacks cancer cells (by binding to CD20) while simultaneously stimulating the immune system (by binding to CD3 on T cells)—it is bispecific.

The goal of this Phase 3 study is to investigate the efficacy and safety of a combination therapy consisting of mosunetuzumab and lenalidomide in adult patients with previously untreated follicular lymphoma. The study compares this novel treatment option with various established standard immunochemotherapies. Patients will be randomly assigned to two groups in a 1:1 ratio. Group 1 (experimental arm) begins with an induction phase in which patients receive one cycle of mosunetuzumab alone over 21 days. This is followed by a combination phase consisting of 11 cycles of 28 days each, during which mosunetuzumab is administered in combination with lenalidomide. Subsequently, the maintenance phase begins with up to 9 additional cycles of 56 days each using the same combination. The total duration of therapy in the experimental arm is up to 30 months. Group 2 (control arm) receives one of the standard therapies: either rituximab or obinutuzumab in combination with CHOP or bendamustine (e.g., R-CHOP, G-CHOP, R-bendamustine, or G-bendamustine). The study is open-label, which means that both the treating physicians and the patients know which therapy is being administered in each case. After completion of the treatment phase, regular follow-up examinations are scheduled to assess the long-term success and tolerability of the therapies. The goal of the study is to determine whether the combination of mosunetuzumab and lenalidomide is a more effective and better-tolerated alternative to standard treatment. Participants will be followed for up to 6 years as part of the study, during which the efficacy of the therapy and the occurrence of side effects from the various medications will be evaluated. A key factor is whether or when the disease progresses again during treatment (progression-free survival).

Women and men aged 18 and older with FL are eligible to participate in this study. The FL must be associated with an increased risk of relapse (calculated using the FLIPI risk calculator, score 2–5), and the patient must not have received any prior treatment for the disease.