Zanubrutinib Plus BR in Newly Diagnosed Symptomatic WM

Inclusion Criteria:

• The gender of the patient is not limited, and the age is ≥18 years old;

• Must meet WM's diagnostic standards;

• The patient is an untreated or patient who has not undergone standard treatment.

• The specific conditions are as follows:

1. No combined chemotherapy with BTKi, BR, RCD, VRD, CHOP and COP

2. No treatment regimen containing fludarabine

3. Chlorambucil or cyclophosphamide for less than 4 weeks (alone or in combinationwith adrenal glucocorticoids)

4. The above treatment did not reach the treatment response (MR)

5. If the above treatment has been applied, the treatment needs to be stopped for 2 weeks before entering the group to start treatment

• The indications for the treatment of indolent lymphoma mainly include (at least oneof the following conditions):

1. Symptomatic hyperviscosity;

2. Symptomatic peripheral neuropathy;

3. Amyloidosis;

4. Cold agglutinin disease; cryoglobulinemia;

5. Disease-related cytopenia (Hb<100 g/L, PLT<100×10^9/L);

6. Giant lymph nodes;

7. Those with systemic systemic symptoms: for two weeks/recurrent fever (above 38℃) and not caused by infection, or Night sweats and/or weight loss >10%within 6 months;

8. The disease progresses rapidly, for example, the lymph nodes increase by morethan 50% within 2 months, and/or peripheral blood lymphocytes absolute valuedoubling time <6 months, and/or rapid hemoglobin or platelet non-autoimmunecauses slow down

9. When there is evidence that the disease has transformed.

• ECOG score ≤ 2 points

• Laboratory examination: neutrophils ≥ 0.75×10^9/L; platelets ≥ 50×10^9/L; totalbilirubin ≤ 2.5 times upper limit; alanine aminotransferase/aspartateaminotransferase ≤3 times upper limit. Creatinine clearance rate ≥ 30ml/min.

• The patient's expected survival time is ≥ 3 months.

Exclusion Criteria:

• Malignant tumors (including active central nervous system lymphoma) other than B-NHLhave been diagnosed or treated within the past year;

• There is clinical evidence that large cell lymphoma transformation has occurred;

• Non-lymphoma-related liver and kidney damage: alanine aminotransferase (ALT)> 3times the upper limit of normal value, aspartate aminotransferase (AST)> 3 times theupper limit of normal value, total bilirubin (TBIL)> upper limit of normal value 2Times, serum creatinine clearance rate <30ml/min;

• Other serious medical conditions will affect the study (such as uncontrolleddiabetes, gastric ulcers, other serious cardiopulmonary diseases, etc.). Thedecision-making power belongs to the researcher;

• Known history of infection with human immunodeficiency virus (HIV) or activehepatitis B virus (HBV) infection, or any uncontrolled active systemic infectionrequiring intravenous antibiotics.

• Central nervous system dysfunction with clinical manifestations or central invasion (Bing-Neel syndrome);

• Patients who have undergone major surgery (not including lymph node biopsy) withinthe past 14 days or expected major surgery during treatment;

• Inability to swallow capsules or suffer from malabsorption syndrome, diseases thatsignificantly affect gastrointestinal function, have undergone gastric or smallbowel resection, symptomatic inflammatory bowel disease or ulcerative colitis,partial or complete intestinal obstruction.

• Need to receive strong cytochrome P450 (CYP) 3A inhibitor treatment.

• Women who are pregnant or breastfeeding, women of childbearing age who have nottaken contraception;

• Allergy to the drugs used.