Zanubrutinib, Bendamustine, Rituximab Prev. Untreated WM

The purpose of this study is to determine the very good partial response (VGPR) or better rate in participants with Waldenström macroglobulinemia (WM). The names of the study drugs involved in this study are as follows: zanubrutinib, bendamustine, and rituximab.

Inclusion Criteria: * Clinicopathological diagnosis of waldenström macroglobulinemia (WM) per the second international workshop on waldenström macroglobulinemia (IWWM2) criteria * Presence of any MYD88 and CXCR4 mutation status, including MYD88 L265P mutation plus CXCR4 wild type, MYD88 L265P mutation plus CXCR4 mutation, or MYD88 wild type * Meeting criteria for treatment per IWWM2 criteria. At least one of the following: * Constitutional Symptoms (at least one of the following) * Recurrent fever * Night sweats * Fatigue * Weight loss * Progressive or symptomatic lymphadenopathy or splenomegaly * Hemoglobin ≤ 10 g/dL * Platelet count ≤ 100 k/uL * Hyperviscosity syndrome * Symptomatic peripheral neuropathy * Systemic amyloidosis * Renal insufficiency * Symptomatic cryoglobulinemia or cold agglutinemia * Treatment naive; must have not received any prior systemic therapy for WM * Participants with suspected or symptomatic hyperviscosity (e.g. nosebleeds, headaches, blurred vision) must undergo plasmapheresis prior to treatment initiation. * Adults age ≥18 * ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A) * Women of childbearing potential: Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or practice complete abstinence1 from heterosexual intercourse during treatment and for at least 1 week after the last dose of zanubrutinib or at least 12 months after the last dose of rituximab, whichever is later. FCBP must be referred to a qualified provider of contraceptive methods if needed. Also, FCBP must have a pregnancy check with a negative serum pregnancy test obtained 28 days prior to and confirmed by C1D1. * Men must agree to use a condom during sexual contact with a female of childbearing potential (FCBP) even if they have had a successful vasectomy 1) while participating in the study; and 2) for at least 1 week following the last dose of zanubrutinib. * Participants must meet the following organ and marrow function as defined below: * Absolute neutrophil count ≥500/mcL believed to be caused by WM bone marrow involvement. Growth factors are not permitted \