Evolving Treatments for Primary Central Nervous System Lymphoma

Primary central nervous system (CNS) lymphoma (PCNSL) is an aggressive form of non-Hodgkin lymphoma that remains confined to the CNS neuroaxis during its natural history of disease and is therefore considered stage IE disease. PCNSL is diffuse large B-cell lymphoma (DLBCL) morphology in more than 95% of patients and is designated primary diffuse large B-cell lymphoma of the CNS on the basis of the 2017 World Health Organization classification of hematopoietic and lymphoid tumors. Rapidly evolving therapeutic paradigms have been linked to evidence of progress in PCNSL, a disease long considered to be incurable. Increasing evidence supports the need for efficient diagnosis, staging, and initiation of therapy, ideally at centers with experience with this type of brain cancer. High-dose methotrexate (MTX) remains a cornerstone of induction regimens, and most data support the use of rituximab. However, clinical research challenges must address key questions, including the development of ever more effective and less toxic induction regimens and the selection of the most appropriate and effective consolidation approaches, as well as the fact that, increasingly, PCNSL affects older patients who do not tolerate strong genotoxic irradiation or high-dose chemotherapy (HDC)-based strategies. Maintenance therapy, immunotherapy, and the implementation of targeted agents on the basis of the molecular and biologic properties of the disease create opportunities for precision medicine and the potential for long-term disease-free survival and cure, with minimal treatment-related neurotoxicity, for a greater fraction of patients.