Orelabrutinib Combined With Rituximab ± Lenalidomide in Response-Adapted Stratified Therapy for Untreated MZL

Inclusion Criteria: 1. Aged ≥18 years, either sex. 2. Histopathologically confirmed CD20-positive marginal zone lymphoma (including MALT, SMZL, and NMZL) with at least 1 measurable lesion. 3. Stage III or IV disease with an indication for treatment. 4. No prior systemic therapy. Patients may have received prior local treatment (including surgery, radiotherapy, anti-Helicobacter pylori therapy, or anti-hepatitis C therapy) if they subsequently progressed, relapsed, or were unsuitable for local therapy. 5. ECOG performance status of 0-2. 6. Adequate organ function meeting the following criteria: 1. Blood count: Absolute neutrophil count ≥1.5×10⁹/L, platelets ≥75×10⁹/L, hemoglobin ≥75 g/L. If bone marrow involvement is present: absolute neutrophil count ≥1.0×10⁹/L, platelets ≥50×10⁹/L, hemoglobin ≥50 g/L. 2. Blood chemistry: Total bilirubin ≤1.5×ULN, AST or ALT ≤2×ULN; serum creatinine ≤1.5×ULN; serum amylase ≤ULN. 7. Coagulation: International normalized ratio (INR) ≤1.5×ULN. 8. Expected survival ≥12 months. 9. Voluntary provision of written informed consent before trial screening. Exclusion Criteria: 1. Current or history of other malignancies, unless treated with curative intent and without evidence of recurrence or metastasis within the past 5 years. 2. Central nervous system involvement or transformation to high-grade lymphoma. 3. Uncontrolled or significant cardiovascular diseases, including: 1. New York Heart Association (NYHA) Class II or higher congestive heart failure, unstable angina, myocardial infarction within 6 months prior to the first study drug dose, or arrhythmia requiring treatment at screening; left ventricular ejection fraction (LVEF) \<50%. 2. Primary cardiomyopathy (e.g., dilated, hypertrophic, arrhythmogenic right ventricular, restrictive, or unclassified cardiomyopathy). 3. History of clinically significant QTc interval prolongation, or QTc interval \>470 ms (female) or \>450 ms (male) at screening. 4. Symptomatic coronary artery disease or subjects requiring medication for it. 5. Poorly controlled hypertension (defined as failure to achieve target blood pressure after ≥1 month of lifestyle modification combined with an adequate, tolerable regimen of ≥3 antihypertensive drugs including a diuretic, or requiring ≥4 antihypertensive drugs for control). 4. Active bleeding within 2 months prior to screening, current use of anticoagulants, or any condition deemed by the investigator to indicate a clear bleeding tendency. 5. History of deep vein thrombosis or pulmonary embolism within the past 6 months. 6. History of organ transplantation or allogeneic bone marrow transplantation. 7. Major surgery within 6 weeks or minor surgery within 2 weeks prior to screening. Major surgery requires general anesthesia (diagnostic endoscopy excluded). Insertion of vascular access devices is exempt. 8. Active infection or uncontrolled HBV (HBsAg positive and/or HBcAb positive with positive HBV DNA), HCV Ab positive, HIV/AIDS, or other serious infectious diseases. (Active infection is defined as requiring systemic antimicrobial therapy or associated with systemic signs/symptoms of inflammation.) 9. Current conditions severely impairing pulmonary function, such as pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, or drug-related pneumonia. 10. Prior treatment with BTK inhibitors, BCR pathway inhibitors (e.g., PI3K, Syk inhibitors), or BCL-2 inhibitors. 11. Pregnancy, lactation, or unwillingness to use effective contraception in subjects of childbearing potential. 12. Concomitant use of moderate/strong cytochrome P450 CYP3A inhibitors or strong inducers. 13. Any other condition considered by the investigator to make the subject unsuitable for trial participation.