[Novel Treatment for Primary Central Nervous System Lymphoma].

Abstract

Primary central nervous system lymphoma (PCNSL) is a form of aggressive extranodal lymphoma confined to the central nervous system. Outcomes have substantially improved thanks to the introduction of high-dose methotrexate-based induction chemotherapy and consolidation strategies (including autologous stem cell transplantation); however, therapeutic challenges remain, particularly in elderly patients and those with relapsed or refractory disease. Recent genomic studies have indicates that PCNSL is characterized by frequent MYD88 and CD79B mutations, resulting in constitutive activation of the B-cell receptor and NF-κB signaling pathways, concurrent with an immunosuppressive tumor microenvironment. These insights provide a rationale for the development of targeted therapies and immunotherapies. Bruton's tyrosine kinase inhibitors and immunomodulatory drugs have shown promising activity in both relapsed and frontline settings, and are currently being evaluated in combination with maintenance strategies. CD19-directed chimeric antigen receptor T-cell therapy and CD20×CD3 bispecific antibodies have also emerged as potential therapeutic options for relapsed/refractory PCNSL, with encouraging efficacy and manageable toxicity profiles. This review summarizes the molecular pathogenesis of PCNSL, current standard treatments, and recent advances in targeted therapies and immunotherapeutic strategies that could improve treatment outcomes.