To evaluate the efficacy and safety of Genetic subtype-matched targeted therapy in the treatment of treatment-naive diffuse large B-cell lymphoma with TP53 mutation.

Using Genetic subtype-matched targeted therapy as first-line treatment for patients with treatment-naive diffuse large B-cell lymphoma (DLBCL) harboring TP53 mutations. The specific Genetic subtype-matched targeted therapy regimen is as follows:

For patients with the MCD/BN2 subtype: Pola-R-CHP + orelabrutinib; For patients with other subtypes: Pola-R-CHP

Inclusion Criteria:

1. Patients aged 18 years and older, up to 70 years.

2. Participants must be able to understand and willing to sign the written informed consent form.

3. Eastern Cooperative Oncology Group performance status 0 to 3.

4. Life expectancy ≥3 months (as determined by the investigator).

5. Pathologically (histologically or cytologically) confirmed treatment-naive CD20-positive diffuse large B-cell lymphoma.

6. Measurable disease defined by PET-CT as a short-axis diameter of at least ≥1.5 cm.

7. Bone marrow and organ function meeting the following criteria (without blood transfusion, G-CSF, or medication correction within 14 days prior to screening):

   Bone marrow function: Absolute neutrophil count ≥1.5×10⁹/L, platelet count ≥80×10⁹/L, hemoglobin ≥80 g/L.

   Liver function: Total serum bilirubin ≤1.5×ULN (≤3.0×ULN if liver metastases present); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN (≤5.0×ULN if liver metastases present).

   Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time ≤1.5×ULN.

   Renal function: Serum creatinine ≤1.5×ULN or estimated creatinine clearance ≥60 mL/min (for males: Cr (mL/min) = (140 - age) × body weight (kg) / [72 × serum creatinine concentration (mg/dL)]; for females: Cr (mL/min) = (140 - age) × body weight (kg) / [85 × serum creatinine concentration (mg/dL)]).

8. Females of childbearing potential must agree to use highly effective contraceptive methods during the treatment period and for 5 weeks after the last dose of study drug. Sexually active males must agree to use highly effective contraception during the treatment period and for 3 months after the last dose.

9. No difficulty swallowing oral tablets/capsules.

10. Good compliance and willingness to adhere to visit schedules, dosing schedules, laboratory tests, and other examination procedures.

Exclusion Criteria:

1. Patients who have previously received systemic anti-tumor therapy.

2. Patients with central nervous system involvement.

3. Patients who received systemic adrenal corticosteroids for more than 5 days within 14 days prior to study drug administration, or who require daily doses of >10 mg of dexamethasone or equivalent drugs to control central nervous system disease.

4. Active concurrent malignancy requiring active treatment.

5. Uncontrolled or severe cardiovascular disease, including (but not limited to) any of the following: congestive heart failure (NYHA class III or IV); myocardial infarction; unstable angina; or presence of arrhythmia requiring treatment at screening, with left ventricular ejection fraction (LVEF) < 50% within 6 months prior to the first dose; primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, undefined cardiomyopathy); clinically significant history of QTc prolongation, second-degree type II atrioventricular block or third-degree atrioventricular block, or QTc interval (Fridericia's method) > 470 ms (female) or > 480 ms (male); atrial fibrillation; patients with uncontrolled hypertension considered unsuitable for participation in the study.

6. Uncontrolled infection or infection requiring intravenous antibiotic therapy.

7. Chronic hepatitis B carriers with active hepatitis B or hepatitis C infection (hepatitis B: acute hepatitis B, untreated chronic hepatitis B virus infection, HBV-DNA ≥ the detection limit of the respective center; hepatitis C: HCV RNA positive) or syphilis. Note: Inactive hepatitis B surface antigen (HBsAg) carriers, subjects with active HBV infection and sustained HBV suppression (HBV DNA < detection limit of the respective center), and subjects cured of HCV may be enrolled.

   Human immunodeficiency virus (HIV) infection.

8. Clinically significant gastrointestinal abnormalities that may affect drug intake, transport, or absorption (such as active gastrointestinal inflammation, chronic diarrhea, intestinal obstruction, etc.), or patients with total gastrectomy, gastric banding surgery, or tumor involvement of the gastrointestinal tract.

9. Patients with a history of bleeding disorders, or patients requiring long-term oral anticoagulation due to comorbidities.

10. Female subjects who are currently pregnant or breastfeeding.

11. Allergy to the study drug or excipients.

12. Patients with active psychiatric disorders, alcohol dependence, drug dependence, or substance abuse.

13. Presence of any life-threatening disease, medical condition, or organ system dysfunction that, in the investigator's opinion, may affect patient safety or compliance with study procedures.

14. Other conditions that, in the investigator's opinion, make the patient unsuitable for participation in this clinical trial.