Inclusion Criteria:
1. Patients with DLBCL who are diagnosed according to the 2021 NCCN Guidelines for B-cell Lymphoma, aged ≥18 years;
2. Don't received treatment;
3. Measurable lesions: at least 1 lymph node lesion \> 1.5 cm in longest dimension, or at least 1 extranodal lesion \> 1.0 cm in longest dimension, and at least 2 measurable lesions accurately measured vertical diameter;
4. Clinical stage II (not suitable for local radiotherapy), III, IV (Ann Arbor stage); Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;
5. Intermediate-high-risk /high-risk group: International Prognostic Index (IPI) score 3-5, aa-IPI score 2-3 or NCCN-IPI score ≥4;
6. Expression of MYC, BCL-2 and BCL-6 (detected by immunohistochemistry, qualitative or quantitative detection), or MYD88, CD79A/CD79B \[9\] and TP53 genetic abnormality \[10\];
7. Patients with non-bone marrow invasion:
1. The absolute value of neutrophils≥1.5×109/L
2. Platelets ≥100×109/L (judged by the investigator according to the condition, the minimum can be ≥75×109/L)
3. Hemoglobin ≥ 90g/L;
9\. The level of biochemical indicators meets the following requirements:
1. Renal function: endogenous creatinine clearance rate \> 30ml/min;
2. Liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal range (ULN); total bilirubin ≤ 2 × ULN (unless Gilbert syndrome is diagnosed);
3. Coagulation function: international normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5×ULN; 9. life expectancy ≥ 3 months; 10. The patient and family members agree and sign an informed consent form.
Exclusion Criteria:
1. Lymphoma with central nervous system invasion or mediastinal large B-cell lymphoma, diagnosis or treatment of malignant tumors other than DLBCL;
2. Cannot tolerate zanubrutinib treatment, or have hypersensitivity reactions to any components of the study drug;
3. Significant cardiovascular disease, including:
1. Myocardial infarction within 6 months prior to screening;
2. Unstable angina pectoris occurring within 3 months prior to screening;
3. Clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes);
4. QTc (corrected by Fridericia formula): \>450ms in men, \>470ms in women, or other ECG abnormalities, including history of second-degree type II atrioventricular (AV) block or third-degree AV block;
5. Any grade 3 or 4 heart disease as defined by the New York Heart Association (NYHA) functional class;
6. Echocardiography (ECHO) showing left ventricular ejection fraction (LVEF) ≤40% (AHA, 2022);
7. Uncontrolled hypertension at screening, manifested as systolic blood pressure ≥180 mmHg and diastolic blood pressure ≥110 mmHg on at least two consecutive blood pressure measurements;
4. Requires continuous treatment with strong or moderate CYP3A inhibitors/inducers. Patients are not eligible if they have taken strong or moderate CYP3A inhibitors/inducers within 7 days prior to the first dose of study drug (or have taken these drugs for less than 5 half-lives);
5. Hepatitis B virus (HBV-DNA) ≥ 1x10\^3 copies/mL or HBV-DNA \> 200 IU/mL or active hepatitis C virus (HCV), or human immunodeficiency virus (HIV) Serologically positive;
6. Obvious bleeding tendency, such as a history of stroke, intracranial hemorrhage within 6 months, or a history of surgery within 4 weeks;
7. Serious infectious diseases at the same time;
8. Refuse to take reliable contraceptive methods during pregnancy, lactation or appropriate age;
9. Participate in another clinical trial of lymphoma treatment at the same time;
10. Unsuitable for enrollment by the investigator.
