Current and emerging therapies for primary central nervous system lymphoma

Primary central nervous system (CNS) lymphoma (PCNSL) is a rare type of extranodal lymphoma exclusively involving the CNS at the onset, with diffuse large B-cell lymphoma (DLBCL) as the most common histological subtype. As PCNSL is a malignancy arising in an immune-privileged site, suboptimal delivery of systemic agents into tumor tissues results in poorer outcomes in PCNSL than in non-CNS DLBCLs. Commonly used regimens for PCNSL include high-dose methotrexate-based chemotherapy with rituximab for induction therapy and intensive chemotherapy followed by autologous hematopoietic stem cell transplantation or whole-brain radiotherapy for consolidation therapy. Targeted agents against the B-cell receptor signaling pathway, microenvironment immunomodulation and blood-brain barrier (BBB) permeabilization appear to be promising in treating refractory/relapsed patients. Chimeric antigen receptor-T cells (CAR-T cells) have been shown to penetrate the BBB as a potential tool to manipulate this disease entity while controlling CAR-T cell-related encephalopathy syndrome. Future approaches may stratify patients according to age, performance status, molecular biomarkers and cellular bioinformation. This review summarizes the current therapies and emerging agents in clinical development for PCNSL treatment.