eligibility_summary
Eligible: adults ≥18 with untreated WM (IWWM2), any MYD88/CXCR4, and need for therapy per IWWM2 (symptoms/organ compromise: B symptoms, cytopenias, hyperviscosity, neuropathy, renal/amyloid, cryo/cold agglutinins). ECOG ≤2, adequate organ/bone marrow, contraception, plasmapheresis if hyperviscosity. Exclude: pregnancy, CNS WM, active infections (HIV/HBV/HCV), immunosuppression/autoimmune cytopenias, recent live vaccine/surgery, major CV/bleeding risk, strong CYP3A inducer, poor compliance/swallowing.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 2 single-arm trial in untreated Waldenström macroglobulinemia testing: 1) Zanubrutinib—oral covalent small‑molecule Bruton tyrosine kinase (BTK) inhibitor. 2) Bendamustine—IV alkylating chemotherapeutic causing DNA crosslinks. 3) Rituximab—IV anti‑CD20 monoclonal antibody. Targets/pathways: BTK-mediated B‑cell receptor/MYD88 signaling with downstream NF‑κB in WM lymphoplasmacytic (CD20+) cells (zanubrutinib), CD20 on malignant/normal B cells driving depletion via ADCC/complement/apoptosis (rituximab), DNA in proliferating tumor cells causing cell‑cycle arrest/apoptosis (bendamustine). Strategy: combine BTK blockade with B‑cell depletion and cytotoxic DNA damage, includes patients regardless of MYD88/CXCR4 status.