Advances in CNS lymphoma

Abstract

Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin lymphoma restricted to the brain, spinal cord, cerebrospinal fluid and eye, in the absence of systemic disease. PCNSL is a diffuse large B-cell lymphoma in greater than 95% of the cases. There has been significant progress in the treatment for this disease and therapeutic regimens have been evolving. Prompt diagnosis and early institution of therapy are essential for improved outcomes. Age and performance status are two important prognostic factors in this disease and patients should be stratified based on these factors in order to establish the best therapeutic approach. High-dose methotrexate based multi-drug chemotherapy is the standard of care induction treatment of newly diagnosed PCNSL. The role of rituximab in upfront therapy is uncertain due to conflicting results from two randomized studies. Consolidation regimens to reduce recurrence risk include thiotepa-based high-dose chemotherapy and autologous stem cell transplant, non-myeloablative chemotherapy alone or whole brain radiation. Delayed neurocognitive side effects are higher with radiation regimens particularly in older patients. Approximately 50% of the patients with PCNSL develop recurrent disease and 10% to 30% of patients have primary refractory disease that are challenging to treat. More insight into the pathophysiology of PCNSL has led to development of clinical trials with novel targeted agents and immunotherapies based on the molecular properties of the disease, that have demonstrated early evidence of activity in the recurrent and refractory setting. Current research is focused on the development of effective and less neurotoxic strategies for prolonged disease-free survival.