Is reduced-dose radiation therapy plus obinutuzumab (drug) at least as effective as standard radiation therapy plus rituximab (drug) for early-stage follicular lymphoma?

Follicular lymphoma (FL) is a malignant disease of the lymphatic system and is classified as a type of non-Hodgkin lymphoma. It is characterized by the uncontrolled proliferation of B lymphocytes. Lymphocytes are a type of white blood cell that is part of the immune system. Symptoms of the disease may include fatigue, anemia, weight loss, fever, night sweats, and swollen lymph nodes. The causes of this disease are not fully understood, but genetic and immunological factors play a role. Radiation therapy is the standard treatment option for stage 1, 2, and 3a FL. In this treatment, the affected lymph nodes are irradiated, causing the cancer cells located there to die. To reduce the radiation dose and the associated side effects, combination therapy with the antibody rituximab may be considered. The radiation dose is measured in grays (Gy); the total dose is administered in several portions (“fractionated”). Studies to date show that the response rate with reduced-dose radiation therapy alone is insufficient. However, there is evidence suggesting that a reduced radiation dose could achieve comparably good results when radiation therapy is combined with immunotherapy. This could result in fewer potential side effects while maintaining the same therapeutic effect.

The goal of the FORTplus study is to investigate the effect of a lower radiation dose (4 Gy) in combination with obinutuzumab compared to the standard treatment of 24 Gy of radiation therapy with rituximab in a larger number of patients. This Phase 3 study has two arms, meaning patients are randomly assigned to one of them. Group 1 receives the standard therapy consisting of 12 radiation treatments of 2 Gy each (total 24 Gy) and rituximab. Group 2 receives 2 radiation treatments of 2 Gy each (total of 4 Gy) plus obinutuzumab. Rituximab and obinutuzumab are antibodies that recognize a specific receptor (CD20) on the surface of cancer cells and then destroy them. Both drugs are already approved for the treatment of FL. The study is open-label, meaning that both the medical staff and the patient know which treatment is being administered. Treatment as part of the study lasts for approximately 4 months, during which the effectiveness of the therapy and the occurrence of side effects are evaluated. The key factor is whether or when the disease progresses again during treatment. The primary endpoint of the study is the response rate to therapy after 18 weeks, which is assessed via computed tomography (CT) or PET-CT. The follow-up period lasts up to 2.5 years in total. Patients aged 18 and older with untreated stage 1, 2, or 3a FL are eligible to participate in the study. The lymphoma must not have spread to tissues or organs outside the lymph nodes.