Subjects who met the inclusion/exclusion criteria were included in the experimental group after signing the informed consent form. One course of Z(R)-MTX(TMZ) treatment was given. After the results of the second-generation sequencing were reported, selinisol was added to the original treatment plan for those with TP53 mutations, and the original treatment plan was continued for those without TP53 mutations. Each course of treatment lasts for three weeks. A mid-term assessment is conducted after three courses of treatment, and a final assessment is carried out after six courses of treatment. After the mid-term or final assessment:

If the PR is not achieved or the disease progresses at any time, the subjects are withdrawn from the group and receive salvage treatment.

If the subjects achieve CR or PR, they enter maintenance treatment and continue with zanubrutinib for 2 years. For young patients (< 65 years old), they can choose whether to receive ASCT as consolidation treatment according to their personal will, and then follow up and observe until 3 years have passed.

SD/PD patients receive subsequent treatment after being judged by the researchers

Inclusion Criteria:

• Have a full understanding of this study and voluntarily sign the informed consent form.
• Untreated patients with primary central nervous system lymphoma (PCNSL) confirmed by pathology (immunotyping) according to the 2016 WHO classification of lymphoid neoplasms.
• Diffuse large B-cell lymphoma (DLBCL) originating from the central nervous system (CNS) without involvement of other organs, confirmed by PET-CT or contrast-enhanced CT.
• Expected survival greater than 3 months.
• Laboratory test results meeting all of the following:
• Creatinine clearance rate ≥ 50 mL/min (calculated by the Cockcroft-Gault formula).
• International normalized ratio (INR) ≤ 1.5 × ULN or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. Patients on warfarin may have INR 2-3.
• Left ventricular ejection fraction (LVEF) ≥ 50%.
• Glomerular filtration rate (GFR) ≥ 60 mL/min.
• Male or female patients of childbearing potential must agree to use effective contraception (e.g., double-barrier methods, condoms, oral or injectable contraceptives, intrauterine device) during the study and for 30 days after the last dose.
• Postmenopausal women (> 45 years old and amenorrheic > 1 year) or surgically sterilized women are exempt from this requirement.

Exclusion Criteria:

• Contraindication to any drug included in the treatment regimen.
• History of clinically significant liver disease, including viral or other hepatitis or cirrhosis.
• Hepatitis B: Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with HBV-DNA above ULN.
• Active hepatitis C: Positive HCV antibody with detectable HCV-RNA.
• Human Immunodeficiency Virus (HIV) infection.
• Congestive heart failure (New York Heart Association Class > II) or history within 6 months of acute myocardial infarction, unstable angina, stroke, or transient ischemic attack.
• Hereditary long QT syndrome or QTc > 480 ms (QTc calculated using Fridericia's formula, QTcF = QT / RR^0.33).
• Other malignancies within 5 years, except: completely cured cervical carcinoma in situ, basal cell carcinoma of the skin, breast carcinoma in situ, or another primary cancer that has been cured and not recurred within 5 years.
• Pregnant or lactating women, or women planning pregnancy during the study period.
• History of significant neurological or psychiatric disorders, including substance or psychotropic-drug abuse.
• Clinically significant active infection.
• Inability to take or swallow oral medication, or conditions affecting drug absorption (e.g., chronic diarrhea, intestinal obstruction).