Inclusion Criteria:
Patients must meet all of the following inclusion criteria:
1. Male or female patients, 18 years of age or older.
2. Multiple myeloma diagnosed according to standard IMWG criteria
3. Patients must have measurable disease defined by at least one of the following five measurements:
* Serum M-protein 1 g/dL (10 g/L).
* Urine M-protein 200 mg/24 hours.
* Serum free light chain assay: involved free light chain level at least 100 mg/L), provided that the serum free light chain ratio is abnormal.
* A biopsy proven evaluable plasmacytoma
* Bone marrow plasmacytosis \> 30% of total marrow cells
4. Patients received one or two prior lines of therapy which must have included bortezomib, lenalidomide-and daratumumab.
5. Patients must meet the following clinical laboratory criteria:
* Absolute neutrophil count (ANC) ≥1,000/mm3 and platelet count≥75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days of enrollment.
* Total bilirubin ≤1.5 the upper limit of the normal range (ULN).
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 ULN.
* Calculated creatinine clearance ≥15 mL/min note: Patients with creatinine clearance of 15-50 mL/min will receive pomalidomide at a reduced dose (3 mg), which may subsequently be increased if well tolerated.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
7. Female patients who:
* Are postmenopausal for at least 24 months before the screening visit, OR
* Are surgically sterile, OR
* Who are of childbearing potential, and agree to practice two effective methods of contraception (1 highly effective method and 1 additional effective method) AT the same time, from the time of signing the informed consent through 90 days after the last dose of study treatment, OR agree to completely abstain from heterosexual intercourse, AND
* Must also adhere to the guidelines of the pomalidomide pregnancy prevention program Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 milli International Units /mL (milli international units) within 10 to 14 days of initiation of Cycle 1 and again within 24 hours of starting Cycle 1. FCBP must also agree to ongoing pregnancy testing. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
8. Male patients, even if surgically sterilized (i.e., status postvasectomy), who:
* Agree to completely abstain from heterosexual intercourse, OR
* Agree to practice effective barrier contraception (i.e., latex condom) during sexual contact with a FCBP, even if they have had a successful vasectomy, throughout the entire study treatment period and through 4 months after the last dose of study treatment AND
* Must also adhere to the guidelines of the pomalidomide pregnancy prevention program.
9. Must be able to take concurrent aspirin 100mg daily (or enoxaparin 40 mg subcutaneously daily \[or its equivalent\] if allergic to aspirin) as prophylactic anticoagulation.
10. 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.
11. Patient is willing and able to adhere to the study visit schedule and other protocol requirements.
Exclusion criteria:
Patients meeting any of the following exclusion criteria are not eligible to participate in the study:
1. Patient underwent an allogeneic transplantation
2. Female patients who are lactating or pregnant.
3. Major surgery within 14 days before enrollment.
4. Central nervous system involvement
5. Concomitant use of any other antineoplastic treatment with activity against MM (with the exception of ≤40 mg Dexamethasone per day or equivalent for no longer than 4 days).
6. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before enrollment
7. Diagnosis of Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
8. 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.
9. Anti-myeloma therapy as follows prior to screening bone marrow aspiration:
* Targeted therapy, epigenetic therapy, within 14 days or at least 5 half-lives,whichever is less;
* Monoclonal antibody treatment for multiple myeloma within 21 days;
* Cytotoxic therapy within 14 days;
* Proteasome inhibitor therapy within 14 days;
* Immunomodulatory agent therapy within 7 days.
* Radiotherapy within 14 days (with the exception of radiotherapy for spinal cord compression or for pain control that should be discussed and approved by the sponsor- investigator prior to study enrollment). However, if the radiation portal covered ≤5% of the bone marrow reserve, the subject is eligible irrespective of the end date of radiotherapy.
10. Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of Cytochrome P450, family 3, subfamily A- clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole or strong Cytochrome P450, family 3, subfamily A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort within 14 days before enrollment in the study.
11. Ongoing or active systemic infection, active hepatitis B virus infection, active hepatitis C infection, or known human immunodeficiency virus (HIV) positive.
12. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
13. Psychiatric illness/social situation that would limit compliance with study requirements.
14. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
15. Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or known GI disease or planned gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment.
16. Diagnosed or treated for another malignancy within 2 years before enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
17. Failure to have fully recovered (ie, Grade 1 toxicity) from the reversible effects of prior chemotherapy.
18. Patient has Grade 3 peripheral neuropathy during the screening period.
19. Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.
20. Patients that have previously been treated with ixazomib or pomalidomide
