This is a prospective, multicenter Phase 2 clinical trial named the MALT-RO study, evaluating ultra-low-dose radiation therapy followed by orelabrutinib as first-line treatment for adults with Stage I-II MALT lymphoma. The study aims to determine the efficacy and safety profile of this sequential regimen. Eligible participants aged 18 years or older with histologically confirmed MALT lymphoma, measurable lesions, no prior systemic anti-lymphoma therapy, adequate organ function, and an ECOG performance status of 0-1 will receive 4Gy ultra-low-dose radiation (2Gy daily for 2 consecutive days) followed by oral orelabrutinib 150mg once daily for up to 6 cycles (28 days per cycle). Patients with partial response or stable disease after 6 cycles may continue orelabrutinib monotherapy for up to 12 cycles or until disease progression. All participants will undergo regular safety monitoring, tumor assessments, and long-term follow-up every 3 months to evaluate treatment durability. This treatment strategy is designed to improve efficacy and achieve more favorable outcomes compared with standard approaches for MALT lymphoma, while minimizing treatment-related toxicities such as long-term organ damage, xerostomia, cataracts, and other complications related to conventional standard-dose radiation, thereby offering a well-tolerated, convenient, targeted therapeutic option for patients with MALT lymphoma under strict ethical oversight in accordance with the Declaration of Helsinki and Chinese Good Clinical Practice guidelines.

Inclusion Criteria:

1. Age ≥ 18 years, all genders eligible;

2. Histopathologically confirmed MALT lymphoma (extranodal marginal zone lymphoma) with at least one measurable lesion outside the spleen, with any diameter > 1.0 cm;

3. No prior systemic anti-tumor therapy after diagnosis (including chemotherapy, targeted therapy, rituximab, etc.).

   Note: For patients with primary gastric MALT lymphoma, Helicobacter pylori (HP) must be negative or the patient must have failed standard HP eradication therapy. Patients with MZL who progressed or relapsed after local treatment (including surgery, Helicobacter pylori eradication, and hepatitis C treatment) are eligible for enrollment.

4. ECOG performance status score of 0-1;

5. Presence of treatment indications as judged by the investigator (including symptoms, cytopenias, risk of end-organ damage, bulky disease, or persistent progression);

6. Adequate major organ function, meeting the following criteria:

   1. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, platelets ≥ 75 × 10⁹/L, hemoglobin ≥ 75 g/L; If bone marrow involvement is present: ANC ≥ 1.0 × 10⁹/L, platelets ≥ 50 × 10⁹/L, hemoglobin ≥ 50 g/L;
   2. Total bilirubin ≤ 1.5 × ULN, AST or ALT ≤ 2 × ULN, serum creatinine ≤ 1.5 × ULN, serum amylase ≤ ULN;
   3. International Normalized Ratio (INR) ≤ 1.5 × ULN.

7. Expected survival ≥ 3 months;

8. Voluntarily provide written informed consent before screening.

Exclusion Criteria:

1. Current or history of other malignant tumors, except for those who have achieved complete remission after radical treatment;

2. Lymphoma involvement of the central nervous system or transformation to high-grade lymphoma;

3. Patients with other tumors who have not recovered from non-hematologic toxicities of prior anti-tumor therapy to ≤ Grade 1 (except for alopecia);

4. Uncontrolled or significant cardiovascular diseases, including:

   1. Congestive heart failure of New York Heart Association (NYHA) Class II or above, unstable angina, myocardial infarction within 6 months before the first dose of the study drug, or arrhythmias requiring treatment at screening, or left ventricular ejection fraction (LVEF) < 50%;
   2. Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, or unclassified cardiomyopathy);
   3. History of clinically significant QTc interval prolongation, or QTc interval at screening > 470 ms for females or > 450 ms for males;
   4. Subjects with symptomatic coronary artery disease requiring medication;
   5. Uncontrolled hypertension (despite lifestyle modification and use of a reasonable and tolerable maximum dose of 3 or more antihypertensive drugs [including diuretics] for more than 1 month, blood pressure still not reaching target, or blood pressure can only be effectively controlled with 4 or more antihypertensive drugs);

5. Active bleeding within 2 months before screening, or currently receiving anticoagulant drugs, or considered by the investigator to have a clear bleeding tendency;

6. Urine protein ≥ 2+ and 24-hour urine protein quantification ≥ 2 g/24 hours;

7. History of deep vein thrombosis or pulmonary embolism within the past 6 months;

8. History of organ transplantation or allogeneic hematopoietic stem cell transplantation;

9. Major surgery within 6 weeks before screening or minor surgery within 2 weeks before screening. Major surgery is defined as surgery performed under general anesthesia; however, diagnostic endoscopic procedures are not considered major surgery. Insertion of vascular access devices is exempt from this exclusion criterion;

10. HIV/AIDS or other serious infectious diseases;

11. Patients with severe pulmonary function impairment due to pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-induced pneumonitis, or other conditions;

12. Previous treatment with BTK inhibitors, BCR pathway inhibitors (e.g., PI3K, Syk), or BCL-2 inhibitors;

13. Subjects with drug abuse or alcohol abuse;

14. Pregnant or lactating women, or subjects of childbearing potential who are unwilling to use contraceptive measures;

15. Other conditions that, in the opinion of the investigator, make the subject unsuitable for participation in this trial.