Inclusion Criteria:

• Male or female patients aged 18 years or older.
• Must have a confirmed diagnosis of MM requiring therapy according to IMWG criteria.
• ECOG performance status of 0 to 2.
• Must have had a relapse or PD after having received 2 or more prior lines of systemic therapy.
  • Note: A line of therapy is defined as 1or more cycles of a planned treatment program; this may consist of 1 or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous SCT, followed by maintenance is considered 1 line of therapy [1]. Typically, each line of therapy is separated by PD. Discussion with the medical monitor may help clarify the number of lines of therapy that a prospective study participant had.
• Must be refractory to lenalidomide, defined as having received at least 2 consecutive cycles of lenalidomide as a single agent or within a lenalidomide-containing regimen and having had PD during treatment with or within 60 days after the last dose of lenalidomide. The starting dose of lenalidomide should have been 25 mg (or as low as 10 mg in the case of renal function impairment or other safety concern), and the final dose should have been a minimum of 10 mg.
• Must have received at least 2 consecutive cycles of a bortezomib- or carfilzomib-containing regimen, and either:
  • Achieved at least a PR and did not have PD during treatment with or within 60 days after the last dose of bortezomib or carfilzomib; OR
  • Had bortezomib and/or carfilzomib intolerance (defined as discontinuation because of drug-related AEs before completion of the planned treatment course) without PD before the start of the next regimen.
• Patients must have measurable disease defined by:
  • Serum M-protein ≥1 g/dL (≥10 g/L); OR
  • Urine M-protein ≥200 mg/24 hours and must have documented MM isotype by immunofixation (central laboratory).
• Patients must meet all of the following clinical laboratory criteria:
  • Absolute neutrophil count (ANC) ≥1000/mm3 and platelet count ≥75,000/mm3, without growth factor or transfusion support;
  • Total bilirubin ≤1.5 times the upper limit of normal (ULN);
  • Alanine aminotransferase and aspartate aminotransferase ≤3×ULN;
  • Calculated creatinine clearance ≥0 mL/min (see Section 9.4.15.1).
• Female patients who:
  • Are postmenopausal for at least 1 year before the Screening Visit; OR
  • Are surgically sterile; OR
  • If they are of childbearing potential, agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method at the same time, for 4 weeks before signing the informed consent through 90 days after the last dose of study therapy; OR
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together); AND
  • In women of childbearing potential (if randomized to Arm B), agree to have 2 negative pregnancy tests before initiating therapy, with 1 or both being a serum test (the first test should be performed within 10-14 days before; the second, within 24 hours before); then have a negative pregnancy test weekly during the first month and monthly thereafter in women with regular menstrual cycles or every 2 weeks thereafter in women with irregular menstrual cycles; and have a negative pregnancy test 4 weeks after the last dose of study therapy.
• Male patients, even if surgically sterilized (ie, status postvasectomy) who:
  • Agree to practice effective barrier contraception during the entire study Treatment period and through 90 days after the last dose of study therapy; OR
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.); AND
  • Do not donate semen or sperm during treatment and for 90 days after the last dose of study therapy.
• Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
• Suitable venous access for the study-required blood sampling, including PK sampling.
• Patient is willing and able to adhere to the study visit schedule and other protocol requirements including blood sampling and bone marrow aspiration.
• Recovered (ie, ≤Grade 1 nonhematologic toxicity) from the reversible effects of prior anticancer therapy.
• Patients must be willing and able to adhere to pomalidomide-related risk mitigation activities if randomized to the pom+dex arm (e.g., REMS, pregnancy prevention programs).

Exclusion Criteria:

• Patients must not have received prior ixazomib or pomalidomide and must not have been a participant in a previous ixazomib clinical study.
• Prior allogenic bone marrow transplantation in any prior line of therapy or prior autologous SCT in the last prior line of therapy—unless the autologous SCT was performed a year or more before disease progression.
• Female patients who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
• Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol, such as life-threatening illness unrelated to cancer.
• Diagnosed with or treated for another malignancy within 2 years before randomization, or previously diagnosed with another malignancy and have any evidence of residual, persistent, or recurrent disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Diagnosis of smoldering MM, Waldenström’s macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
• Known allergy to any of the study medications or their analogues, or excipients in the various formulations.
• Peripheral neuropathy Grade 1 with pain or Grade 2 or higher peripheral neuropathy of any cause on clinical examination during the Screening period.
• Treatment with any investigational products or with chimeric or fully human monoclonal antibodies within 30 days before randomization, systemic anticancer therapy or radiotherapy within 14 days before randomization.
  • Note: “spot” radiation for areas of pain is permitted, and major surgery within 14 days before randomization.
• Known gastrointestinal disease or gastrointestinal procedure that could interfere with the oral absorption or tolerance of study therapy, including difficulty swallowing.
• Serious infection requiring parenteral antibiotic therapy or any other serious infection within 14 days before randomization.