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

Inclusion Criteria: \[1\] Newly diagnosed PCNSL confirmed by histopathology, or independently relapsed SCNSL (diffuse large B-cell lymphoma), diagnosed according to the 2016 WHO diagnostic criteria. \[2\] Signed written informed consent, and ability to comply with protocol-specified visits and related procedures. \[3\] Cranial MRI (non-contrast + contrast) performed within 28 days prior to study enrollment must show at least one measurable lesion in two perpendicular dimensions (according to the 2014 Lugano criteria). \[4\] ECOG performance status of 0-4. \[5\] Adequate organ and bone marrow function, defined as follows: 1. Hematology: Absolute neutrophil count (ANC) ≥ 1.0×10⁹/L, platelet count (PLT) ≥ 50×10⁹/L, hemoglobin (HGB) ≥ 8.0 g/dL; no administration of granulocyte growth factors, platelet transfusion, or red blood cell transfusion within 7 days prior to testing. 2. Liver function: Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN. 3. Renal function: Serum creatinine (Cr) ≤ 1 × ULN or creatinine clearance (CCr) ≥ 90 mL/min. 4. Cardiac function: Cardiac function class below Grade III (NYHA criteria); echocardiography shows left ventricular ejection fraction (LVEF) ≥ 50%. 5. Coagulation: International normalized ratio (INR) ≤ 1.5 × ULN, activated partial thromboplastin time (APTT) ≤ ULN + 10 s, and prothrombin time (PT) ≤ ULN + 3 s. 6. Thyroid function: Baseline thyroid-stimulating hormone (TSH) level within normal range, or abnormal baseline TSH with normal T3/T4 and no associated symptoms. \[6\] Life expectancy \> 3 months. \[7\] Age ≥ 18 years. \[8\] Female subjects of childbearing potential or male subjects with female partners of childbearing potential must use effective contraception throughout the treatment period and for 90 days after the last dose. Exclusion Criteria: 1. Presence of disease involvement outside the central nervous system. 2. History of a second primary malignancy (except for adequately treated non-melanoma skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, intramucosal carcinoma of the gastrointestinal tract, or breast carcinoma that has been cured and has shown no recurrence within the past 5 years). 3. History of allergic disease, severe drug allergy, or known hypersensitivity to macromolecular protein preparations or any component of the PD-1 monoclonal antibody injection formulation. 4. Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies, or CAR-T cell therapy (or any other antibody targeting T-cell co-stimulation or checkpoint pathways). 5. Previous allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. 6. Planned to receive other systemic anti-tumor therapies during the study period. 7. Use of anti-cancer vaccines or other immunostimulatory anti-tumor therapy within 3 months before the first dose. 8. Severe acute or chronic infection requiring systemic therapy. 9. Active, known, or suspected autoimmune disease (refer to Appendix 5), or history of such disease within the past 2 years (patients with vitiligo, psoriasis, alopecia, or Graves' disease not requiring systemic treatment in the past 2 years, hypothyroidism requiring only thyroid hormone replacement, or type 1 diabetes requiring only insulin replacement may be enrolled). 10. Use of immunosuppressive drugs within 4 weeks prior to the first study treatment, excluding intranasal, inhaled, or other local glucocorticoids or physiologic doses of systemic glucocorticoids (i.e., no more than 10 mg/day prednisone or equivalent). 11. Positive human immunodeficiency virus antibody (HIV-Ab), active hepatitis, or other uncontrolled infectious diseases. 12. Current or previous history of idiopathic pulmonary fibrosis or idiopathic pneumonia. 13. Known active tuberculosis. 14. Previous history of grade ≥3 immune-related adverse events from prior immunotherapy. 15. History of definite neurological or psychiatric disorders. 16. Administration of any live vaccine against infectious diseases within 4 weeks before the first dose or planned use during the study period (e.g., influenza vaccine, chickenpox vaccine, etc.). 17. Clear history of alcohol or drug abuse. 18. Pregnancy or lactation. 19. Participation in other investigational drug studies with active treatment within 1 month before the first dose. 20. Any other condition that, in the investigator's judgment, may affect the evaluation of efficacy or safety in this study.