ZR2 Versus R2 Regimen in the Treatment of Newly Diagnosed Follicular Lymphoma

Inclusion Criteria: 1. Voluntarily participate in the clinical study; fully understand and comprehend this study and sign the Informed Consent Form (ICF); willing to follow and capable of completing all study steps; 2. According to the 5th edition of the WHO classification of hematological and lymphoid tumors, diagnosed as CD20+ classic FL (grade 1-3a FL) by histology, and no previous anti-FL treatment has been received; 3. Age ≥ 18 years; 4. Judged by the investigator, the subject must urgently need to receive systemic treatment, based on meeting at least one GELF criterion; 5. At least one measurable lesion \[longest diameter (LDi) ≥ 15mm, lymph node lesion LDi ≥ 10mm, evaluated according to the 2014 Lugano efficacy criteria\]; 6. The subject has at least one measurable target lesion: i. PET/CT scan shows positive PET lesion, or ii. CT scan or MRI shows \> 1 measurable lymph node lesion (long axis \> 1.5 cm) or \> 1 measurable extranodal lesion (long axis \> 1.0 cm); 7. ECOG performance status is 0-2; 8. Expected survival period \> 3 months; 9. Adequate organ function and bone marrow function, without severe heart, lung, liver, kidney and immune deficiencies (no blood transfusion, granulocyte colony-stimulating factor or other medical support drugs within 7 days before starting this study): hemoglobin (HB) ≥ 60 g/L; absolute neutrophil count (ANC) ≥ 5×109/L; platelets (PLT) ≥ 50×109/L; aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 5×ULN; total bilirubin (TBIL) ≤ 1.5×ULN; creatinine clearance rate (Ccr) ≥ 40 ml/min (estimated by Cockcroft-Gault formula); left ventricular ejection fraction (LVEF) ≥ lower limit of normal value. 10. Patients with reproductive potential must agree to use effective contraceptive measures (dual methods, such as condom + oral contraceptive), and avoid pregnancy or make their partners pregnant during the treatment period and within 12 months after the last administration. Exclusion Criteria: 1. The subject has a history of systemic anti-leukemia treatment for FL (including any curative radiotherapy for the purpose of cure); 2. The subject has a history of aggressive B-cell lymphoma or has currently undergone histological transformation to DLBCL; 3. FL 3b; 4. The subject had suspected or confirmed primary CNS tumor at screening or had evidence of known CNS involvement; 5. The subject has a history of severe allergic reaction or immediate severe allergic reaction to any component or excipient of zanubrutinib, lenalidomide, or rituximab; 6. Has other tumors that affect the study medication or interfere with the results; 7. Received live vaccine within 28 days before treatment; 8. Has reproductive capacity and is unwilling to use effective contraceptive measures; 9. Pregnant or lactating women; 10. Known human immunodeficiency virus (HIV) infection, or any serological status indicating active hepatitis B or hepatitis C virus infection: 1) HBV DNA positive. Positive for hepatitis B surface antigen (HBsAg) or serologically positive for hepatitis B core antibody (HBcAb), if HBV DNA is undetectable and is willing to undergo monthly HBV reactivation monitoring, then can be enrolled. 2) HCV antibody positive. For patients with HCV antibody, if HCV RNA is undetectable, then can be enrolled; 11. Severe coagulation disorders and severe damage to organs such as heart, brain, lungs, liver, and kidneys; 12. Had a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the past 12 months; has any life-threatening disease, medical condition, or organ system dysfunction that the subject considers may affect the safety of the subject or cause study risks.