tirabrutinib + methotrexate + temozolomide + rituximab

This is a **combination regimen** comprising **tirabrutinib** (a potent, selective second-generation Bruton's tyrosine kinase inhibitor), **high-dose methotrexate** (an antimetabolite chemotherapeutic), **temozolomide** (an oral alkylating agent), and **rituximab** (a monoclonal antibody targeting CD20 on B lymphocytes). This regimen is under evaluation for the treatment of **primary central nervous system lymphoma (PCNSL)**, particularly in newly diagnosed patients. Tirabrutinib specifically inhibits Bruton's tyrosine kinase, blocking B-cell receptor signaling and suppressing malignant B-cell proliferation and survival. Methotrexate inhibits dihydrofolate reductase, disrupting DNA synthesis. Temozolomide alkylates/methylates DNA, leading to tumor cell death. Rituximab selectively targets CD20-positive B-cells, mediating cell lysis via immune effector mechanisms. This multi-agent combination leverages both targeted and cytotoxic mechanisms and is studied as an induction regimen in clinical research for PCNSL[2][6].

Other names

tirabrutinib + methotrexate + temozolomide + rituximab