Ibrutinib + Venetoclax in Untreated WM

Inclusion Criteria: * Participants must meet the following criteria on screening examination to be eligible to participate. Screening evaluations including consent, physical exam, and laboratory assessments will be done within 30 days prior to Cycle 1 Day 1. Bone marrow biopsy \& aspirate, and CT C/A/P will be done within 90 days prior to Cycle 1 Day 1. * Clinicopathological diagnosis of Waldenström macroglobulinemia \[28\]. * Known tumor expression of mutated MYD88 performed by a CLIA certified laboratory. * Symptomatic disease meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenström macroglobulinemia \[29\]. * Participants with symptomatic hyperviscosity (e.g. nosebleeds, headaches, blurred vision) must undergo plasmapheresis prior to treatment initiation. * Age ≥ 18 years * ECOG performance status ≤2 (see Appendix A) * Measurable disease, defined as presence of serum immunoglobin M (IgM) with a minimum IgM level of \>2 times the upper limit of normal of each institution is required * At the time of screening, participants must have acceptable organ and marrow function as defined below: * Absolute neutrophil count ≥500/uL (no growth factor permitted) * Platelets ≥50,000/uL (no platelet transfusions permitted) * Hemoglobin ≥ 7 g/dL (transfusions permitted) * Total bilirubin \< 1.5 x institutional ULN * AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN * Estimated GFR ≥30 mL/min * Females of childbearing pote…