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

Exclusion Criteria20

• Presence of disease involvement outside the central nervous system.
• 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).
• 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.
• 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).
• Previous allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Planned to receive other systemic anti-tumor therapies during the study period.
• Use of anti-cancer vaccines or other immunostimulatory anti-tumor therapy within 3 months before the first dose.
• Severe acute or chronic infection requiring systemic therapy.
• 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).
• 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).
• Positive human immunodeficiency virus antibody (HIV-Ab), active hepatitis, or other uncontrolled infectious diseases.
• Current or previous history of idiopathic pulmonary fibrosis or idiopathic pneumonia.
• Known active tuberculosis.
• Previous history of grade ≥3 immune-related adverse events from prior immunotherapy.
• History of definite neurological or psychiatric disorders.
• 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.).
• Clear history of alcohol or drug abuse.
• Pregnancy or lactation.
• Participation in other investigational drug studies with active treatment within 1 month before the first dose.
• Any other condition that, in the investigator's judgment, may affect the evaluation of efficacy or safety in this study.