selinexor + methotrexate + rituximab

A combination therapy consisting of **selinexor**, **methotrexate** (typically high-dose), and **rituximab**. Selinexor is an oral, first-in-class, selective inhibitor of nuclear export (SINE) targeting the protein exportin-1 (XPO1/CRM1). By inhibiting XPO1, selinexor causes nuclear retention and activation of multiple tumor suppressor proteins, triggering apoptosis in malignant cells and also inhibiting NF-κB signaling. Methotrexate is a folate analog that inhibits enzymes involved in nucleotide synthesis, chiefly dihydrofolate reductase, leading to blockade of DNA synthesis and cell division. Rituximab is a monoclonal antibody that targets the CD20 antigen on B lymphocytes, leading to cell lysis via immune-mediated mechanisms. This combination regimen is under investigation for newly diagnosed primary or secondary central nervous system lymphoma (CNSL) in patients who are not eligible for autologous stem cell transplantation. The rationale is that selinexor enhances sensitivity to chemotherapy and radiotherapy in hematologic malignancies, methotrexate provides cytotoxic activity against lymphoma cells, and rituximab confers immunotherapeutic benefit against CD20-positive B-cells. This approach aims to offer an effective, less toxic option for CNSL patients unable to tolerate more intensive chemotherapeutic regimens[1][2][6][7].