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

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.