This study is a prospective, open-label, single-arm phase II clinical study to evaluate the safety and efficacy of zanubrutinib plus R-CHOP (ZR-CHOP) as the first-line therapy for newly diagnosed diffuse large B-cell lymphoma patients with high-risk factors.

Inclusion Criteria:

1. Histologically confirmed DLBCL patients have one of the following risk factors(including but not limited to double expression, extranodal involvement, high ki67, bulky)；
2. Age ≥ 18 years old;
3. At least one measurable lesion (defined as lymph node lesion ≥15mm, extra-segmental lesions ≥ 10mm);
4. ECOG performance status 0-2;
5. Functions of major organs meet the following conditions: Echocardiography left ventricular ejection fraction ≥50%; Creatinine clearance ≥30 ml/min; ALT and AST≤3 times the normal range；
6. Hematopoietic function should meet the following conditions: Platelet count ≥50×109/L; Hemoglobin ≥ 8.0g /dL; Absolute count of neutrophil (ANC)≥1.0×109/L;
7. Expected survival of ≧3 months

Exclusion Criteria:

1. Major surgery within 4 weeks before treatment;
2. Severe organ dysfunction(including but not limited to complications of uncontrolled cardiovascular diseases, blood clotting disorders, connective tissue diseases, serious infectious diseases and other diseases);
3. Patients who cannot cooperate with treatment or follow-up on time.
4. Pregnant or lactating females;
5. any uncontrolled active systemic infection requiring intravenous (IV) antibiotics;
6. There was a history of other active malignant diseases within the 2 years prior to study entry, except for: (1) adequately treated cervical carcinoma in situ; (2) local skin basal cell carcinoma or squamous cell carcinoma; (3) previous malignant disease that is under control and has undergone local radical treatment (surgical or other forms).
7. History of severe hemorrhagic disorders, such as hemophilia A, hemophilia B, von Willebrand's disease, or spontaneous bleeding requiring blood transfusion or other medical intervention
8. Human immunodeficiency virus (HIV) infection or the following serological status reflecting the presence of active hepatitis B or C virus infection: a. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) are present. Patients who are HBCAB-positive, HBsAg negative, have no hepatitis b virus (HBV) DNA (< 20 IU/mL), and agree to be monitored for HBV virus reactivation can be enrolled. Antibodies to the hepatitis C virus (HCV) are present. HCV antibody-positive patients with no HCV RNA detected could be included in the group.
9. The presence of any life-threatening disease, medical condition, or organ system dysfunction that the investigator believes may affect the subject's safety or pose a risk to the study.
10. The researchers think it is not suitable to participate in this experiment.