Pirtobrutinib Plus Methotrexate-Based Chemoimmunotherapy for Systemic DLBCL With CNS Involvement

Inclusion Criteria: Patients must satisfy all of the following conditions to be enrolled in this study: 1.Fully understand the study and voluntarily provide written informed consent. 2.Age: 14-80 years old. 3.Estimated survival of more than 3 months as judged by the investigator. 4.Histologically or cytologically / flow-cytometry confirmed B-cell-derived diffuse large B-cell lymphoma (DLBCL). 5.Central nervous system (CNS) involvement: diagnosis is established if any one of the following is present: symptoms related to CNS involvement, abnormal imaging findings, or pathological evidence (positive cerebrospinal fluid (CSF) cytology, positive biopsy of brain parenchymal lesions, or positive CSF-ctDNA). 6.Non-hematologic toxicities related to prior therapy shall have recovered to Grade 1 or baseline (per NCI-CTCAE Version 5.0), alopecia excluded. 7.Bone marrow and organ function meet the following criteria (no blood transfusion, G-CSF administration, or pharmacologic correction within 14 days prior to screening): 1. Bone marrow function: absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L; platelet count ≥ 50 × 10⁹/L; hemoglobin ≥ 60 g/L. 2. Liver function: serum total bilirubin ≤ 1.5 × ULN (≤ 3.0 × ULN in the presence of liver involvement); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5.0 × ULN in the presence of liver involvement). 3. Coagulation function: international normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. 4. Renal function: serum creatinine ≤ 1.5 × ULN or estimated creatinine clearance ≥ 30 mL/min. 5. Calculationformula(Cockcroft-Gault):Male:Cr(mL/min) = (140 - age) × bodyweight (kg) / (72 × serum creatinine(mg/dL))Female:Cr(mL/min) = (140 - age) × body weight (kg) × 0.85 / (72 × serum creatinine (mg/dL)) 8.Women of child-bearing potential and men with reproductive potential have no plan for conception with their partners during the study and for 3 months after treatment discontinuation. They must adopt one of the following effective contraceptive measures throughout the study period and for 3 months after treatment discontinuation: abstinence, physical contraception (e.g., sterilization, condoms), or hormonal contraceptives initiated at least 3 months prior to the first study drug administration. Male subjects shall refrain from sperm donation from treatment initiation through 3 months after treatment discontinuation. The patient or legal guardian voluntarily signs the informed consent form. 9.Good compliance and willingness to adhere to visit schedules, drug administration plans, laboratory tests, and other study procedures. exclusion Criteria: Patients meeting any one of the following criteria will be excluded from this study: 1. Contraindication to any drug in the treatment regimen. 2. History of active liver disease, including viral or other hepatitis, or liver cirrhosis. (Active hepatitis B is defined as HBV-DNA above the upper limit of normal; active hepatitis C is defined as positive HCV antibody. Subjects with positive HCV antibody but negative HCV-RNA are eligible for enrollment.) 3. Human immunodeficiency virus (HIV) infection. 4. Congestive heart failure (New York Heart Association \[NYHA\] functional class \> 2); medical history of acute myocardial infarction, unstable angina pectoris, stroke, or transient ischemic attack within the preceding six months. 5. Congenital long-QT syndrome, or QTc \> 480 ms. (Note: QTc interval shall be calculated by the Fridericia's formula: QTcF = QT/(RR)\^0.33.) 6. Pregnant or breastfeeding women, or subjects planning to become pregnant during the study period. 7. Documented prior history of neurological or psychiatric disorders; or history of psychotropic substance abuse or illicit drug use.