Zanubrutinib, Obinutuzumab Combined With Lenalidomide (ZGR) for the Treatment of Untreated Follicular Lymphoma

Inclusion Criteria: * Gender: No restrictions; age ≥18 years. * Diagnosis: Histologically confirmed CD20-positive follicular lymphoma (FL), Grade 1, 2, or 3A, per 2016 WHO classification. All patients must provide sufficient archived or fresh tumor tissue samples for immunohistochemical (IHC) analysis. * Disease Stage \& Treatment Need: * Stage III or IV disease, or Stage II with bulky disease, meeting at least one of the following criteria: * a) Bulky disease: Lymph node or extranodal (excluding spleen) mass with maximum diameter ≥7 cm. * b) Local symptoms or organ dysfunction due to progressive lymphadenopathy or extranodal tumor mass. * c) B symptoms (fever, night sweats, or unintentional weight loss \>10% of body weight within ≤6 months). * d) Symptomatic extranodal involvement (e.g., pleural/peritoneal effusion). * e) Cytopenias due to bone marrow infiltration (hemoglobin \<10 g/dL, absolute neutrophil count \[ANC\] \<1.0×10⁹/L, platelets \<100×10⁹/L). * f) Involvement of ≥3 lymph nodes, each ≥3 cm in diameter. * g) Symptomatic splenomegaly. * Prior Therapy: No prior systemic therapy for FL. * ECOG Performance Status: ≤2. * Measurable Disease: At least one measurable lesion (\>2 cm in longest diameter by CT/MRI). * Life Expectancy: ≥6 months. * Adequate Organ Function: * a) ANC ≥1.0×10⁹/L (without growth factor support). * b) Platelets ≥50×10⁹/L (untransfused within 7 days). * c) Total bilirubin (TBIL) ≤1.5×ULN. * d) ALT/AST ≤3×ULN. * e) Creatinine clearance ≥30 mL/min (calculated by modified Cockcroft-Gault formula). * Contraception: Men and women of childbearing potential must agree to use highly effective contraception during the study and for 4 weeks after treatment discontinuation. * Informed Consent: Patients must voluntarily participate and sign informed consent forms (ICF). Exclusion Criteria: * Patients meeting any of the following criteria will be excluded from this study: * Histologic evidence of central nervous system (CNS) lymphoma, leptomeningeal lymphoma, or transformation to high-grade lymphoma (e.g., diffuse large B-cell lymphoma, DLBCL). * Grade 3B follicular lymphoma (FL) or transformed FL. * Ann Arbor Stage I FL. * Prior history of malignancy, unless the patient has been disease-free for ≥5 years and the treating physician deems the risk of recurrence low (exceptions: non-melanoma skin cancer, cured localized prostate cancer, carcinoma in situ of the cervix, or squamous intraepithelial lesions on PAP smear). * Use of any investigational drugs, antibiotics, or participation in another interventional clinical trial within 4 weeks prior to enrollment. * Major surgery (excluding lymph node biopsy) within 14 days before enrollment or anticipated need for major surgery during the study. * Prior treatment with zanubrutinib, obinutuzumab, or lenalidomide. * Immunodeficiency or autoimmune disease history, or chronic systemic steroid therapy (\>10 mg/day prednisone equivalent) or immunosuppressive therapy within 7 days before enrollment. * Severe hepatic dysfunction (including severe jaundice, hepatic encephalopathy, refractory ascites, or hepatorenal syndrome), cachexia, or multi-organ failure with renal impairment. * Clinically significant cardiovascular abnormalities: * NYHA Class III/IV heart failure * Myocardial infarction within 6 months before enrollment, Malignant arrhythmias (including QTc ≥480 ms), Uncontrolled hypertension (Systolic blood pressure (SBP) ≥150 mmHg and diastolic blood pressure (DBP) ≥100 mmHg), Unstable angina. Active infections: * HIV, active hepatitis B/C infection (HBV DNA ≥2000 IU/mL or HCV RNA detectable) * Uncontrolled systemic infections. * Bleeding disorders or coagulation abnormalities, or thrombotic events within 3 months. * Severe hypersensitivity to the active ingredients or excipients of the study drugs. * Pregnancy, lactation, or unwillingness to use effective contraception in women of childbearing potential. * Other conditions deemed unsuitable by the investigator.