The bispecific antibody Odronextamab is already approved for follicular lymphoma (FL)—Does the combination with lenalidomide provide additional benefit in patients with previously treated FL or marginal zone lymphoma?

Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are two types of malignant diseases that arise from B cells, a subtype of white blood cells that are part of the immune system. Both are classified as non-Hodgkin lymphomas and affect the lymphatic system, which plays a central role in defending the body against disease. Both are slow-growing B-cell lymphomas, but they differ in their site of origin and certain biological characteristics. FL and MZL arise from B cells, a subgroup of white blood cells that are part of the immune system. Both lymphomas are slow-growing, but differ in their site of origin and certain biological characteristics. Treatment for both conditions depends on the stage (extent of the disease), the patient’s symptoms, and their overall health. Standard therapy usually consists of immunotherapy with rituximab combined with conventional chemotherapy or radiation therapy. In the event of disease recurrence or an inadequate response to therapy (refractory disease), other approaches such as CAR-T cell therapy or treatment with lenalidomide may be used. Lenalidomide works by activating the immune system to attack cancer cells while simultaneously inhibiting the growth of tumor cells. Bispecific antibodies, such as odronextamab, represent a new form of therapy. These can bind to two target structures simultaneously—one on the tumor cell and one on the immune cell—thereby triggering a targeted immune response. There are already a number of drugs of this type that are approved for the treatment of various diseases—odronextamab is already approved for follicular lymphoma.

The goal of the OLYMPIA-5 study is to investigate whether the combination of odronextamab and lenalidomide is more effective and safer than the standard therapy with rituximab and lenalidomide in the treatment of FL or MZL. The drugs (odronextamab, rituximab, lenalidomide) are already approved; however, there is currently no approval for the specific situation and combination in which they are being tested here. The treatment is therefore experimental. In the first part of the study (Phase 1b), all patients will receive only the experimental treatment (odronextamab with lenalidomide) to determine the optimal dose. In the second part (Phase 3), the two treatment options (odronextamab + lenalidomide versus rituximab + lenalidomide) will then be compared using the determined optimal dose. To do this, patients will be randomly assigned to one of the two treatment arms. The study will follow patients for up to 5 years during and after treatment.

Women and men aged 18 and older with follicular lymphoma or marginal zone lymphoma who have already received at least one line of therapy—but for whom that therapy was ineffective (refractory) or who have experienced a relapse—are eligible to participate in the study. The previous treatment should have included a CD20 antibody (e.g., rituximab). The follicular lymphoma must be stage 1–3a, and there must be no brain involvement.