Has active hemolytic anemia, plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, amyloidosis, significant autoimmune, CNS or other malignant disease POEMS syndrome POEMS syndrome or active plasma cell leukemia; POEMS syndrome requiring therapy, previously treated or untreated POEMS syndrome Diagnosed with plasma cell leukemia, POEMS syndrome or amyloidosis. Plasma cell leukemia, primary amyloidosis or POEMS syndrome POEMS syndrome, Plasma cell leukemia, Waldenstrom's macroglobulinemia or Amyloidosis Plasma cell leukemia, primary amyloidosis or POEMS syndrome POEMS syndrome Diagnosis of Waldenstrom's macroglobulinemia, POEMS syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome Diagnosis of smoldering multiple myeloma, Waldenstrom's macroglobulinemia, POEMS syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome Has known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of IXAZOMIB - Diagnosis of smoldering multiple myeloma, Waldenstrom's macroglobulinemia, POEMS syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome Multiple myeloma of IgM subtype, POEMS, plasma cell leukemia Multiple myeloma of IgM subtype, POEMS, plasma cell leukemia Waldenstrom’s macroglobulinemia: must have failed 2 courses of therapy Waldenstrom’s macroglobulinemia or immunoglobulin (Ig)M myeloma Waldenstrom’s macroglobulinemia or immunoglobulin M (IgM) myeloma Clinicopathological diagnosis of Waldenstrom’s macroglobulinemia and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom’s macroglobulinemia (Kyle et al, 2003) or have high risk disease with an serum IgM level of 6,000 mg or higher (Gustine et al, 2016) Clinicopathological diagnosis of Waldenstrom macroglobulinemia, and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom macroglobulinemia Confirmed diagnosis of Marginal Zone Lymphoma or Waldenstroms Macroglobulinemia Waldenstrom’s macroglobulinemia – must have failed 2 courses of therapy Waldenstrom’s macroglobulinemia or IgM myeloma PART I: Patients with Waldenstrom’s macroglobulinemia (WM) must meet the indications for treatment per the International Workshop on Waldenstrom’s Macroglobulinemia (IWWM) PART IB: Patients with Waldenstrom’s macroglobulinemia (WM) must meet the indications for treatment per the International Workshop on Waldenstrom’s Macroglobulinemia (IWWM) Waldenström’s macroglobulinemia Waldenstrom's macroglobulinemia: must have failed 2 courses of therapy Waldenstrom's macroglobulinemia Clinicopathological diagnosis of Waldenstrom’s macroglobulinemia and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom’s macroglobulinemia Clinicopathological diagnosis of Waldenstrom macroglobulinemia and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom macroglobulinemia or serum immunoglobulin M (IgM) > 6000 mg/dL and measurable disease Waldenstrom's macroglobulinemia or immunoglobulin (Ig)M myeloma Waldenstrom's macroglobulinemia must have failed 2 courses of therapy Lymphoplasmacytic lymphoma (LPL), with or without associated Waldenstroms Macroglobulinemia (WM) Waldenstrom's macroglobulinemia Waldenstrom macroglobulinemia Waldenstrom's Macroglobulinemia. Waldenstrom macroglobulinemia immunoplasmacytoma/immunocytoma (Waldenstrom's macroglobulinemia) Clinicopathological diagnosis of Waldenstrom’s macroglobulinemia and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom’s macroglobulinemia Waldenstrom’s macroglobulinemia – must have failed 2 courses of therapy Waldenstrom's macroglobulinemia Waldenstrom's macroglobulinemia. STEP I: Patients with monoclonal gammopathy of undetermined significance or asymptomatic multiple myeloma are not eligible Subjects with only plasmacytomas, plasma cell leukemia, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), non-secretory myeloma or primarily amyloidosis. Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma only Subjects with second malignancies requiring active systemic therapy are excluded; subjects with second malignancies not requiring active systemic therapy or pre-malignant conditions such as monoclonal B-cell lymphocytosis (MBL) or monoclonal gammopathy of undetermined significance (MGUS) may be eligible Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma Monoclonal gammopathy of undetermined significance (MGUS), Waldenstrom’s macroglobulinemia, or asymptomatic (smoldering) myeloma Patient has smoldering multiple myeloma or monoclonal gammopathy of unknown significance (MGUS). Patients with stage I or smoldering myeloma, isolated plasmacytoma, or benign monoclonal gammopathy are not eligible Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma Patients with monoclonal gammopathy of undetermined significance are not eligible Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (presence of serum M-protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the M-protein), or smoldering multiple myeloma (asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage) Diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions Subjects with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), primary amyloidosis, Waldenstrom's macroglobulinemia, or POEMS syndrome (plasma cell dyscrasia with poly neuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) Diagnosed with smoldering MM, monoclonal gammopathy of undetermined significance, Waldenstrom macroglobulinemia, plasma cell leukemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome or amyloidosis Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational; prior therapy with bisphosphonate is allowed; prior radiation therapy to a solitary plasmacytoma is allowed; prior clinical trials or therapy for smoldering MM or monoclonal gammopathy of undetermined significance (MGUS) are allowed but should be discussed with the principal investigator Smoldering myeloma, monoclonal gammopathy of undetermined significance (MGUS), or plasma cell leukemia Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma Monoclonal Gammopathy of Undetermined Significance (MGUS), Waldenstrom's macroglobulinemia, or smoldering myeloma hyperviscosity syndrome due to monoclonal gammopathy Solitary bone or extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia, or monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), primary amyloidosis, Waldenstrom's macroglobulinemia, POEMS syndrome or active plasma cell leukemia Diagnosis of any monoclonal gammopathy: monoclonal gammopathy of undetermined significance (MGUS), asymptomatic / active multiple myeloma, asymptomatic / active Waldenstrom macroglobulinemia (WM) POEMS (Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, or IgM myeloma.