Orelabrutinib Combined With Rituximab as First-line Systemic Treatment for Marginal Zone Lymphoma

Exclusion Criteria23

• Currently or previously having other malignancies, unless there is evidence of no recurrence or metastasis within the past 5 years after curative treatment;
• Lymphoma involvement of the central nervous system or transformation to high-grade lymphoma;
• Non-hematological toxicities from prior anti-cancer treatments not recovered to ≤ Grade 1 (excluding alopecia);
• Presence of uncontrolled or significant cardiovascular disease, including:
• New York Heart Association (NYHA) Class II or higher congestive heart failure, unstable angina, myocardial infarction within 6 months before the first administration of the study drug, or arrhythmias requiring treatment at screening, left ventricular ejection fraction (LVEF) \< 50%;
• Primary cardiomyopathy (such as dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, unclassified cardiomyopathy);
• History of clinically significant QTc interval prolongation, or QTc interval \> 470 ms for females, \> 450 ms for males during the screening period;
• Symptomatic or medically treated coronary artery disease;
• Uncontrolled hypertension (defined as blood pressure not reaching target levels despite a reasonable and tolerable full dose of three or more antihypertensive drugs (including diuretics) for more than one month, or requiring four or more antihypertensive drugs to effectively control blood pressure).
• Active bleeding within 2 months before screening, or currently taking anticoagulant drugs, or deemed by the investigator to have a clear tendency to bleed;
• Urine protein ≥ 2+, and 24-hour urine protein quantification ≥ 2 g/24 hours;
• History of deep vein thrombosis or pulmonary embolism within the past six months;
• History of organ transplantation or allogeneic bone marrow transplantation;
• Major surgery within 6 weeks before screening or minor surgery within 2 weeks before screening. Major surgery is defined as surgery using general anesthesia, but diagnostic endoscopy is not considered major surgery. Insertion of a vascular access device will be exempt from this exclusion criterion;
• Active infection or uncontrolled HBV (HBsAg positive and/or HBcAb positive with positive HBV DNA titer), HCV Ab positive, HIV/AIDS, or other severe infectious diseases;
• Currently having pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, or other conditions that significantly affect pulmonary function;
• Previous treatment with BTK, BCR pathway inhibitors (such as PI3K, Syk), or BCL-2 inhibitors;
• Suitable and preparing for stem cell transplantation;
• Any psychiatric or cognitive impairment that may limit their understanding, execution of the informed consent form, and compliance with the study;
• Subjects with drug abuse or alcoholism;
• Pregnant, breastfeeding women, and fertile subjects unwilling to use contraception;
• Need to continuously take drugs with moderate to severe inhibitory or strong inducing effects on cytochrome P450 CYP3A;
• Any other condition deemed by the investigator as unsuitable for participation in this trial.