Advances in first-line treatment for primary central nervous system lymphoma: highlights from the 2025 ASH annual meeting.

Advances in targeted therapies for newly diagnosed primary central nervous system lymphoma (PCNSL) were a key highlight at the 2025 ASH Annual Meeting. While high-dose methotrexate (HD-MTX) remains the cornerstone of PCNSL treatment, the integration of BTK inhibitors, immunomodulators, and novel agents-such as selinexor and anti-PD-1 antibodies-is reshaping the first-line management paradigm. These emerging combinations are improving response rates and survival, paving the way for more effective strategies. Here, we provide a timely synthesis of these pivotal updates presented at ASH 2025.