Is a reduced-intensity version of the current standard treatment sufficient for central nervous system lymphoma?

Primary central nervous system lymphoma (PCNSL) is a form of blood cancer belonging to the group of non-Hodgkin lymphomas and affects lymphocytes in the brain and/or spinal cord. Lymphocytes are a type of white blood cell that is part of the body’s immune system. The disease can progress rapidly, and its 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, depression, and headaches. The standard treatment consists of intensive chemotherapy with the goal of complete recovery (remission). A commonly used treatment protocol is called the MATRix protocol. It involves up to four cycles of combined immunochemotherapy consisting of rituximab, high-dose methotrexate, high-dose cytarabine, and thiotepa. Due to its intensity, this therapy can be associated with side effects that may have long-term consequences; therefore, it is always a goal of cancer treatment to minimize side effects as much as possible.

The goal of the OptiMATe study (Phase 3 study) is to investigate the efficacy and safety of a de-escalated (modified) therapy compared to the standard MATRix protocol in a larger number of patients. To this end, patients are randomly assigned to two groups. Group 1 receives the reduced regimen with rituximab and high-dose methotrexate (one cycle), followed by two cycles of MATRix therapy. Subsequently, the response to therapy is assessed using magnetic resonance imaging (MRI) of the head. Group 2 receives the standard therapy according to the MATRix protocol, consisting of 4 cycles. A follow-up MRI is performed after cycles 2 and 4. The study is single-blind, meaning only the medical staff knows which medications were administered. Patients are not informed of this. As part of the treatment, the study will evaluate the effectiveness of the therapy and the occurrence of side effects from the administered medications. A key factor is whether or when the disease progresses again during therapy. The primary endpoint of the study is the progression-free survival rate two years after completion of therapy. It is important to note that treatment will continue outside the study in the form of further high-dose chemotherapy. This applies equally to both groups.

Women and men between the ages of 18 and 70 with previously untreated PCNSL are eligible to participate in this study. Participants between the ages of 66 and 70 must meet additional criteria regarding their general health status. The lymphoma must not be detectable in the rest of the body.