Current retrospective studies have demonstrated that achieving deep remission following treatment for Waldenström's macroglobulinemia (WM) correlates with prolonged survival. While the bendamustine-rituximab (BR) regimen or single-agent zanubrutinib are currently recommended as first-line therapies, neither achieves optimal deep remission. Additionally, prolonged zanubrutinib monotherapy may lead to cumulative adverse effects. Therefore, this study aims to evaluate the efficacy and safety of the bendamustine-rituximab-zanubrutinib combination regimen as a first-line treatment option for MYD88-mutated WM patients.

Inclusion Criteria:

1. Previously untreated symptomatic Waldenström macroglobulinemia (WM) meeting IWWM-7 diagnostic criteria:

   1. Presence of monoclonal IgM-type immunoglobulin in serum
   2. Bone marrow infiltration by plasmacytoid lymphocytes or bone marrow biopsy showing small lymphocytes/plasma cells/plasmacytoid lymphocytes (any quantity) in the intertrabecular space
   3. Exclusion of other non-Hodgkin lymphoma subtypes
   4. Typical immunophenotype: CD5-/CD10-/CD19⁺/CD20⁺/CD23-/CD79b⁺ /sIgM⁺/CD138- clonal B-cells. Variant phenotypes may show CD5/CD10/CD23 /CD38 positivity or coexistence of clonal B-cells and plasma cells.

2. MYD88 L265P mutation is detected in peripheral blood or bone marrow.

3. Serum monoclonal IgM ≥5 g/L.

Exclusion Criteria:

1. Co-morbidity of uncontrolled infection or autoimmune disease
2. Co-morbidity of other active malignancy
3. Co-morbidity of uncontrolled heart disease
4. Co-morbidity of severe digestive system disorders precluding oral medication
5. Seropositive for human immunodeficiency virus
6. Hepatitis B virus (HBV)-DNA > 1000 copies/mL
7. Seropositive for hepatitis C (except in the setting of a sustained virologic response)
8. Neutrophil <1×10E9/L, platelet < 75×10E9/L, alanine transaminase (ALT) or aspertate aminotransferase (AST) > 2.5 × upper limit of normal (ULN), total bilirubin > 1.5 × ULN，eGFR < 30 mL/min, or receiving renal replacement therapy.