New immunochemotherapy regimen for lymphomas of the brain or spinal cord (primary CNS lymphoma) in which standard high-dose chemotherapy is not an option

Primary central nervous system lymphoma (PCNSL) is a specific type of non-Hodgkin lymphoma in which the disease manifests in the brain and/or spinal cord. PCNSL affects lymphocytes, a type of white blood cell that is part of the body’s immune system. The disease can progress rapidly, and the exact cause is unknown; however, certain risk factors, such as a weakened immune system, may play a role. Symptoms include, among others, personality changes, dementia, seizures, depression, and headaches. The standard treatment usually consists of intensive immunochemotherapy followed by an autologous stem cell transplant. In this procedure, stem cells are collected from the patient’s blood prior to high-dose chemotherapy and then reinfused so that the bone marrow, which has been damaged by the chemotherapy, can recover. This procedure is a standard treatment for many severe blood cancers, but it differs from what is known as allogeneic stem cell transplantation, in which, following intensive chemotherapy, the patient is not reinfused with their own stem cells but with cells from a donor. This procedure is intended to safely and completely eliminate the patient’s diseased blood cells. The standard therapy is intensive and may not be suitable for patients with pre-existing conditions or older patients. Instead, weaker medications are used, but this worsens the prognosis.

The goal of the MTR² study is to further investigate the efficacy and safety of the combination therapy consisting of methotrexate, tafasitamab, lenalidomide, and rituximab in a selected group of patients. All of these medications are already approved; however, this specific combination could be particularly effective for PCNSL and thus represent an alternative to standard therapy. As part of the study, all patients will receive this combination therapy, which is administered over a period of 84 days (approximately 3 months). At the start, patients will receive two antibodies—tafasitamab (Minjuvi®) and rituximab—via infusion on days 0 and 5. On Day 1, they receive a high-dose infusion of methotrexate, a chemotherapy drug that is particularly effective against lymphomas in the central nervous system. In addition, starting on day 4, patients receive lenalidomide, which supports the immune system and acts against cancer cells. This is administered at a dose of 20 mg daily for the first 21 days and increased to 25 mg starting with the second cycle. It is taken on days 4 through 17 of each of the four treatment cycles. The goal of this therapy is to combat the lymphoma in a targeted and effective manner by combining different mechanisms of action. The first assessment of efficacy takes place after two treatment cycles (primary endpoint of the study). Drug therapy is completed after 84 days. Follow-up care as part of the study continues for one year. The study is open-label, meaning that medical staff and patients know which medications are being taken. Treatment as part of the study lasts for up to 1.5 years, during which the therapy’s efficacy and the occurrence of side effects are evaluated. The key factor is whether or when the disease progresses.

Women and men between the ages of 18 and 99 with a newly diagnosed primary B-cell lymphoma of the central nervous system (PCNSL) who have not yet received treatment and are not eligible for high-dose chemotherapy with stem cell transplantation may participate in the study. Participants aged 70 and older may enroll regardless of their general health status; younger participants must have a compromised health status. Prerequisites include a measurable tumor lesion in the brain or spinal cord, as well as adequate organ function—particularly of the heart, liver, kidneys, and blood count. Individuals with cancer outside the central nervous system, a history of non-Hodgkin lymphoma, certain viral infections (e.g., HIV or hepatitis), or severe infections are excluded. Previous lymphoma treatment (except for steroids or a single dose of methotrexate/rituximab) also excludes participants. Pregnant and breastfeeding women, as well as individuals with serious comorbidities or substance use disorders, are also ineligible to participate. The goal is to evaluate a safe and targeted therapy for this specific patient group.