The following criteria is provided for health care professionals.

Inclusion Criteria:

• Willing to be registered into the pomalidomide (POMALYST®) Risk Evaluation and Mitigation Strategy (REMS®) program
• Enrolled in the MMRF002 Molecular Profiling Protocol (NCT02884102) with report less than 120 days old
• Disease free of prior malignancies for ≥ 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or prostate cancer not requiring therapy
• High risk patients with relapsed refractory multiple myeloma (RRMM), who have:
  • received at least one prior but no more than 3 prior therapies
  • exposed to both a PI and an IMiD
  • had early relapse after initial treatmentEarly relapse as defined by at least one of the following: (Relapse is defined as the IMWG uniform response)
    1. Within 3 years post autologous stem cell transplantation (ASCT) on maintenance, or 18 months if unmaintained
    2. Within 18 months of initial non-ASCT based therapy
• Patients must have progressed after their most recent treatment and require therapy for myeloma
• Females of reproductive potential must have a negative pregnancy test at baseline, be non-lactating, and willing to adhere to scheduled pregnancy testing
• Females of reproductive potential and males must practice and acceptable method of birth control
• Laboratory values obtained ≤ 14 days prior to registration:
  • Absolute neutrophil count (ANC) ≥ 1000/ul
  • Hemoglobin (Hgb) ≥ 8 g/dl
  • Platelet (PLT) ≥ 75,000/ul
  • Total bilirubin <1.5 x upper limit of normal (ULN) or if total bilirubin is >1.5 x ULN, the direct bilirubin must be ≤ 2.0 mg/dL
  • Aspartate aminotransferase (AST) <3 x ULN
  • Creatinine Clearance ≥ 30 mL/min
• Measurable disease of Multiple Myeloma (MM) as defined by at least one of the following:
  • Serum monoclonal protein ≥ 1.0 g by protein electrophoresis
  • ≥ 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
  • Serum immunoglobulin free light chain (FLC) ≥10 mg/dL AND abnormal serum immunoglobulin kappa to lambda FLC ratio
  • Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease)
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2
• Ability to take aspirin, warfarin, or low molecular weight heparin

Sub-Protocol Inclusion Criteria:

Refer to each respective Sub Protocol for additional inclusion criteria.

Exclusion Criteria:

Patients will be ineligible for this study if they meet any one of the following criteria:

• Aggressive multiple myeloma requiring immediate treatment as defined by:
  • Lactate dehydrogenase (LDH) > 2 times ULN
  • Presence of symptomatic extramedullary disease or central nervous system involvement
  • Hypercalcemia >11.5 mg/dl
  • Acute worsening of renal function (CrCl < 30 ml/min) directly related to myeloma relapse
  • Any neurological emergency related to myeloma
  • Clinical symptoms of hyperviscosity related to monoclonal protein
  • Involved serum free light chain > 100 mg/dL (1000 mg/L) in the setting of prior diagnosis of cast nephropathy
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days of enrolment
• Known hypersensitivity or development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide, pomalidomide or similar drug. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of the agents
• Prior Ixazomib/Pomalidomide/Dexamethasone combination therapy
• Pregnant or breast-feeding females
• Serious medical or psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance, interfere in the completion of treatment per protocol, or follow-up evaluation
• Active hepatitis A, B or C viral infection or known human immunodeficiency virus (HIV) infection
• Concurrent symptomatic amyloidosis or plasma cell leukemia
• POEMS syndrome [plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes]
• Residual side effects to previous therapy > Grade 1 prior to initiation of therapy (Alopecia any grade and/or neuropathy Grade 2 without pain are permitted)
• Prior allogeneic or ASCT within 12 weeks of initiation of therapy. Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD)
• Prior experimental therapy within 14 days of protocol treatment or 5 half-lives of the investigational drug, whichever is longer
• Prior anticancer therapy within 14 days of initiation of protocol therapy (Dexamethasone/ 40mg/day) for a maximum of 4 days before screening is allowed
• Prior major surgical procedure or radiation therapy within 4 weeks of the initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy).
• Known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or Gastro Intestinal (GI) absorption of drugs administered orally
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
• Other co-morbidity, which would interfere with patient's ability to participate in trial or that confounds the ability to interpret data from the study

Sub-Protocol Exclusion Criteria:

Refer to each respective Sub Protocol for additional exclusion criteria.