Comparison of combination therapy with mosunetuzumab and lenalidomide versus standard therapies for relapsed or refractory marginal zone lymphoma

Marginal zone lymphoma (MZL) is one of the so-called indolent (slow-growing) non-Hodgkin lymphomas that originate in certain white blood cells, called B cells. There are various subtypes, depending on where the lymphoma originates (e.g., in lymph nodes, the spleen, or other organs such as the stomach). Although it often progresses slowly, the disease may return after treatment (recurrence) or may no longer respond to therapy (refractory). The standard treatment for recurrent or refractory MZL often consists of a combination of different active ingredients. Established therapies include rituximab combined with lenalidomide, bendamustine, or a chemotherapy regimen called CHOP. Rituximab is an antibody that specifically binds to the CD20 surface protein on B cells. Lenalidomide is an immunomodulator that activates the body’s own immune system. Bendamustine and the CHOP regimen consist of chemotherapeutic agents. Despite these options, there are situations in which the disease cannot be adequately controlled. The study drug mosunetuzumab is a bispecific antibody that is injected under the skin (subcutaneously). It binds simultaneously to the cancer cells and to the T cells of the immune system. This specifically directs the body’s own immune cells to the tumor cells and activates them. It is not yet approved for the treatment of MZL in combination with lenalidomide.

The goal of this Phase 3 study is to investigate the efficacy and safety of the combination therapy of mosunetuzumab plus lenalidomide compared to standard therapies. Patients will be randomly assigned to two groups as part of the study. The study arm receives the combination therapy of mosunetuzumab plus lenalidomide. The control arm receives a standard therapy selected by the treating physicians (rituximab + lenalidomide, rituximab + bendamustine, or rituximab + CHOP). The study is open-label, meaning that both medical staff and patients know which treatment is being administered. For the analysis, patients will be divided into different groups based on their diagnosed subtype of MZL and the time to progression or recurrence during initial treatment. The primary endpoint of the study is progression-free survival (PFS) up to 6.5 years, that is, the time from the start of the study until the first occurrence of progression (worsening of the disease), recurrence (return of the disease), or death from any cause.

Women and men aged 18 and older with relapsed or refractory MZL are eligible to participate in this study. They must have already received at least one prior treatment (including an anti-CD20 antibody or ibrutinib) and must not be suitable candidates for radiation therapy or surgery as part of their lymphoma treatment.