A Chemotherapy-Free Treatment Regimen with Venetoclax and Rituximab for Waldenström Macroglobulinemia

Waldenström macroglobulinemia (WM) is a rare cancer of the so-called B cells, specialized immune cells that recognize pathogens and produce antibodies. WM is classified as an “indolent” non-Hodgkin lymphoma. This disease progresses slowly, and many patients initially have few or no symptoms. Treatment is usually not necessary until symptoms appear or the disease significantly worsens. A characteristic feature of WM is the production of large amounts of a specific antibody (IgM), which can cause symptoms such as fatigue, weight loss, anemia, or nerve damage. To date, the disease has typically been treated with a combination of chemotherapy and antibodies such as rituximab, a therapy that is not always well tolerated, especially by older patients. Rituximab is an antibody that specifically binds to a protein on the surface of B cells (CD20). This allows the immune system to recognize and destroy these cells. Venetoclax is another drug used to treat WM. It specifically blocks the BCL-2 protein, which protects cancer cells from dying. This blockade makes the cancer cells “susceptible” again to natural cell death (apoptosis). Both drugs are approved for the treatment of WM.

The goal of this Phase 2 study is to test the combination of venetoclax and rituximab and to determine whether this chemotherapy-free combination is an effective and well-tolerated alternative to standard therapy. In the VIWA-1 study, participants are assigned to the treatment or control group at random (randomized). In addition, the allocation takes into account the presence of certain genetic changes (mutations in MYD88 and CXCR4); this is called stratified randomization. This is intended to ensure that both groups are comparable in terms of key disease characteristics. One group receives the combination of venetoclax and rituximab over a fixed period of twelve months. The comparison or control group receives standard chemotherapy (DRC), which consists of six treatment cycles. A total of 80 patients in Germany, France, and Greece are expected to participate.

Eligible participants include women and men aged 18 and older who have been diagnosed with Waldenström macroglobulinemia and require treatment. A prerequisite is that patients be in generally good health (including adequate heart, liver, and kidney function). Patients with other serious illnesses, active infections, or a history of cancer treatment within the last three years are excluded.