Zanubrutinib Plus GCVP (Obinutuzumab, Cyclophosphamide, Vindesine, Prednisolone) in Previously Untreated Follicular Lymphoma

Inclusion Criteria

1. Participate in the clinical study voluntarily, fully understand and be informed of the study, sign the informed consent in person, willing to follow and be able to complete all test procedures.
2. 18-80 years old (inclusive), all genders.
3. Histopathologically confirmed grade 1-3a follicular lymphoma (FL) at stage III/IV or extensive stage II disease not suitable for radiotherapy, with at least one evaluable lesion (short axis ≥ 1.5 cm), meeting treatment indications according to GELF criteria or having a strong treatment desire.
4. No prior anti-tumor therapy, such as chemotherapy, radiotherapy, immunotherapy or biotherapy (tumor vaccine, cytokine, or growth factor controlling cancer).
5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-3.
6. Adequate bone marrow and organ function, no serious hematopoietic dysfunction, abnormal heart, lung, liver, kidney function and immune deficiency.

   * Blood routine: White blood cell count ≥ 3.0×109/L, Absolute neutrophil count ≥ 1.5×109/L (use of granulocyte colony stimulating factor is permitted), Hemoglobin ≥ 9.0 g/dL (pre-transfusion or use of recombinant human erythropoietin is permitted), Platelet count ≥ 75×109/L (transfusion is permitted to reach this level). If peripheral blood abnormalities are due to lymphoma infiltration of the bone marrow or spleen, enrollment may be considered at the investigator's discretion.
   * Echocardiogram: Left ventricular ejection fraction (LVEF) ≥ 50%.
   * Liver function: serum bilirubin ≤ 2.5 times the upper limit of normal value, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal value (AST is allowed if liver is involved, ALT ≤ 5 times the upper limit of normal value).
   * Renal function: creatinine clearance ≥ 60 mL/min (estimated according to the Cockcroft-Gault formula).
   * Coagulation function: INR ≤ 1.5 times the upper limit of normal value; PT and APTT ≤ 1.5 times the upper limit of normal value.
7. Life Expectancy of at least 6 months.
8. Men and women of childbearing potential must use contraception during the study and for at least 90 days after the last dose of study medication.

Exclusion Criteria

1. Central nervous system involvement secondary to lymphoma.
2. Known severe allergic reactions to humanized or murine monoclonal antibodies, or known contraindications to any drug in the regimen.
3. History of other active malignant diseases within 2 years prior to study entry, but eligibility for inclusion: a) adequately treated carcinoma in situ of the cervix; b) local basal cell carcinoma or squamous cell carcinoma of skin; c) Pre-existing malignant disease that is under control and has undergone local radical treatment (surgical or other forms).
4. History of Human Immunodeficiency Virus (HIV) infection and/or other acquired Immunodeficiency syndrome. During screening period, patients with hepatitis B virus (HBV) surface antigen or hepatitis C virus (HCV) antibody positive must further test HBV DNA (no more than 2000 iu/ml) and HCV RNA (not exceed the method detection limit). Those ruling out active HBV or HCV infection are permitted to participate in the study. Carriers of the HBV, those with stable HBV after treatment or cured of HCV are also allowed to be enrolled.
5. Any active infections, including but not limited to bacterial, fungal or viral infections, that require systemic anti-infective treatment within 14 days prior to initiation treatment.
6. Major surgery was performed within 28 days prior to initiation treatment.
7. Combined with severe or uncontrolled disease, including but not limited to congestive heart failure, uncontrolled hypertension, unstable angina, active peptic ulcer, severe hemorrhagic diseases (such as hemophilia, von willebrand disease) or spontaneous bleeding.
8. History of stroke or intracranial hemorrhage within 6 months prior to initiation treatment.
9. Continuous treatment with strong and moderate CYP3A inhibitors or CYP3A inducers is required.
10. History of severe neurological or psychiatric disorders, including but not limited to dementia or epilepsy.
11. Conditions related to drug abuse or medical, psychological and social issues that may interfere with study participation or outcome evaluation.

    Investigator Discretion: Any patient deemed unsuitable for enrollment by the investigator.
12. Patients deemed unsuitable for the study by investigators.