A study of belimumab in combination with rituximab and venetoclax compared with treatment with rituximab and venetoclax in patients with chronic lymphocytic leukemia (CLL)

Chronic lymphocytic leukemia (CLL) is a type of cancer that spreads slowly and affects lymphocytes, a type of white blood cell. A very similar form is small lymphocytic lymphoma (SLL). Lymphocytes are divided into B cells and T cells; both are normally responsible for defending the body against pathogens. In chronic lymphocytic leukemia, abnormal B cells are produced in increased numbers and spread throughout the body. Treatment for CLL (SLL) has improved significantly in recent years, particularly through drugs such as rituximab and venetoclax, which specifically target cancer cells. The antibody rituximab binds to a surface protein on B cells (CD20), while venetoclax inhibits the so-called Bcl-2 protein. As a result, both drugs selectively induce the death of B cells.

The BeliVeR study is testing a combination of these proven drugs with belimumab, an antibody that modulates the immune system and is already approved for other conditions. Belimumab works by blocking a protein called BAFF, which promotes the survival of malignant B cells and reduces their sensitivity to treatment. Although many patients benefit from rituximab/venetoclax treatment, there are some who do not respond to it or who experience severe side effects due to the long duration of therapy. By combining belimumab with rituximab and venetoclax, the study aims to improve the efficacy of treatment in individuals with refractory or relapsed CLL and to achieve earlier and more durable therapeutic success. To this end, participants will be divided into two study arms: one group will receive rituximab and venetoclax, while the other will also receive belimumab. Assignment will be random and open-label, meaning that both the patient and the physician are aware of the group assignment. If fewer than one tumor cell per 10,000 white blood cells is detectable in a person, they are considered MRD-negative. The study compares how quickly and how many participants in each study arm achieve this level of disease-free status. The study consists of several treatment cycles lasting a total of 2 years, during which participants will be examined regularly.

Eligible participants are adult patients with a confirmed diagnosis of CLL or small lymphocytic lymphoma (SLL) who have not responded to previous treatments or in whom the disease has recurred. In addition, participants should require treatment due to symptoms such as an enlarged spleen or lymph nodes.