New Combination Therapy for Older Patients with Aggressive B-Cell Lymphoma

Aggressive B-cell lymphomas are a group of non-Hodgkin lymphomas that typically progress rapidly and are therefore referred to as “aggressive.” They affect B lymphocytes, a subtype of white blood cells that are part of the body’s immune system. The most common form is diffuse large B-cell lymphoma (DLBCL). In DLBCL, rapid enlargement of the lymph nodes and involvement of various organs can be observed. Other symptoms include fever, night sweats, and weight loss, among others. The exact cause of DLBCL is unknown, but genetic mutations and infections such as the Epstein-Barr virus may play a role. Patients with newly diagnosed DLBCL are typically treated with a combination of chemotherapy and immunotherapy, such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). However, these treatments may be too risky for older patients or those with certain comorbidities, highlighting the need for less burdensome therapies that are still effective. Glofitamab and polatuzumab vedotin are new drugs that have already been approved for the treatment of lymphomas. These drugs work differently. While glofitamab is a so-called bispecific antibody that simultaneously binds to both the malignant lymphoma cells and the body’s immune cells, thereby effectively combating the lymphoma cells, polatuzumab vedotin binds to the lymphoma cells and delivers an active substance into the cell interior that kills the affected cells. These drugs therefore act in a highly targeted manner. Rituximab is an antibody that has been used for many years to treat lymphoma.

The goal of this Phase 2 study is to further investigate the efficacy and safety of a combination therapy consisting of rituximab, polatuzumab vedotin, and glofitamab (R-Pola-Glo) in a selected group of older patients. All of these drugs are already approved for the treatment of DLBCL, but not in combination or as first-line therapy. All patients will receive the same treatment, and the study is open-label, meaning that both the medical staff and the patients know which drugs are being administered. Treatment as part of the study will initially last for 12 months, followed by a follow-up period of up to 54 months, during which the efficacy of the therapy and the occurrence of side effects from the various drugs will be evaluated. A key factor is whether or when the disease progresses again during treatment. The treatment consists of several cycles. The primary endpoint of the study is the progression-free survival rate after 12 months.

Patients over the age of 60 with aggressive B-cell lymphoma are eligible to participate in this study. The disease must not have been previously treated.