PD-1 Inhibitor Combined With Rituximab, Methotrexate, and Orelabrutinib (PD-1i+RMO) for Newly Diagnosed PCNSL and SCNSL.

This study tests a new combination of immunotherapy (a PD-1 inhibitor drug) with standard drugs — rituximab, methotrexate, and orelabrutinib — for newly diagnosed primary central nervous system lymphoma (PCNSL) or secondary CNS lymphoma (SCNSL), which are cancers occurring in the brain and spinal cord. **You may be eligible if...** - You are 18 or older - You have a newly diagnosed PCNSL (lymphoma confined to the brain/nervous system) confirmed by biopsy, or a separately relapsed SCNSL (diffuse large B-cell lymphoma) - Your brain MRI (within 28 days of enrollment) shows at least one measurable lesion - Your overall performance status is adequate (ECOG 0-4) - Your blood counts and organ function meet required levels - Your life expectancy is more than 3 months **You may NOT be eligible if...** - Your lymphoma has spread outside the central nervous system - You have previously been treated with anti-PD-1/PD-L1 immunotherapy or CAR-T therapy - You have active autoimmune disease or are on immunosuppressive drugs - You have a positive HIV test, active hepatitis, or another serious uncontrolled infection - You are pregnant or breastfeeding - You have a current or prior history of pulmonary fibrosis or lung inflammation Talk to your doctor to see if this trial is right for you.