A study to evaluate the efficacy and safety of mosunetuzumab in combination with lenalidomide, compared with rituximab in combination with lenalidomide, in patients with follicular lymphoma

Follicular lymphoma originates from so-called B cells, a subtype of white blood cells responsible for defending the body against pathogens. It is a slow-growing but difficult-to-treat disease that often responds to chemotherapy but also frequently recurs. Treatment is tailored to the individual; a combination of chemotherapy and an antibody, such as rituximab, is frequently used. In many cases of relapsed or refractory follicular lymphoma, treatment with rituximab and lenalidomide is successful. Lenalidomide is an immunomodulatory drug, meaning it enhances the immune system’s function and helps it fight cancer cells. Rituximab binds to the CD20 protein, which is found on the surface of B cells, thereby triggering cell death. The study drug mosunetuzumab is a new type of antibody—a so-called bispecific antibody—that can bind to two cell receptors simultaneously: First, it binds to B cells via the CD20 cell receptor and then, via the other receptor (CD3), attracts and binds to another type of immune cell, the T cells. By binding to both cell types, the T cells are better able to recognize and attack the tumor cells. The CELESTIMO study is investigating the efficacy and safety of the combination of mosunetuzumab and lenalidomide compared to the combination of rituximab and lenalidomide. In particular, progression-free survival—the time until the disease progresses—will be compared up to 8 years after the start of the study. To this end, participants are divided into 3 groups; assignment is random and open-label (everyone knows which group they are in). A participant in one study arm will receive mosunetuzumab and lenalidomide over 12 cycles (cycle 1: 21 days; cycles 2–12: cycle: 28 days) of mosunetuzumab and lenalidomide, while the second group receives the combination of lenalidomide and rituximab over 12 cycles (same cycle lengths). The third group is a U.S. extension group that also receives the same treatment regimen as Group 1. In rare cases, an inflammatory reaction known as cytokine release syndrome may occur in response to treatment and is then treated with tociluzumab. Eligible participants include all individuals with relapsed or refractory follicular lymphoma who have received at least one prior line of treatment. The lymphoma must be histologically documented and express CD20 on the tumor cells.