The following criteria is provided for health care professionals.

Inclusion Criteria:

1. Histologically confirmed MM with measurable disease per IMWG guidelines as defined by at least 1 of the following:
   1. Serum M-protein ≥ 0.5 g/dL (> 5 g/L) by serum protein electrophoresis (SPEP) or for immunoglobulin (Ig) A myeloma, by quantitative serum IgA levels; or
   2. Urinary M-protein excretion at least 200 mg/24 hours; or
   3. Serum free light chain (FLC) ≥ 100 mg/L, provided that the serum FLC ratio is abnormal.
2. Had at least 1 prior anti-MM regimen and no more than 3 prior anti-MM regimens. Induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 anti-MM regimen.
3. Documented evidence of progressive MM (based on the Investigator's determination according to the modified IMWG response criteria) on or after their most recent regimen.
4. Prior treatment with bortezomib or other Proteasome Inhibitor (PI) is allowed, provided all of the following criteria are met:

5. Best response achieved with prior bortezomib at any time was ≥ PR and with the last PI (PI therapy (alone or in combination) was ≥ PR, AND Participant did not discontinue bortezomib due to ≥ Grade 3 related toxicity, AND Must have had at least a 6-month PI-treatment-free interval prior to Cycle 1 Day 1 (C1D1) of study treatment.

6. Resolution of any clinically significant non-hematological toxicities (if any) from previous treatments to ≤ Grade 1 by C1D1.
7. Adequate hepatic function within 28 days prior to C1D1
8. Adequate renal function within 28 days prior to C1D1
9. Adequate hematopoietic function within 7 days prior to C1D1

Exclusion Criteria:

1. Has received selinexor or another XPO1 inhibitor previously.
2. Prior malignancy that required treatment, or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to randomization.
3. Any concurrent medical condition or disease (e.g., uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, etc.) that is likely to interfere with study procedures.
4. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1.
5. Active plasma cell leukemia.
6. Documented systemic light chain amyloidosis.
7. MM involving the central nervous system.
8. Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome.
9. Spinal cord compression.
10. Greater than Grade 2 neuropathy or ≥ Grade 2 neuropathy with pain at baseline, regardless of whether or not the patient is currently receiving medication
11. Intolerance, hypersensitivity, or contraindication to glucocorticoids.
12. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks prior to C1D1. Localized radiation to a single site at least 1 week before C1D1 is permitted. Glucocorticoids within 2 weeks of C1D1 are permitted. Patients on long-term glucocorticoids during screening do not require a washout period but must be able to tolerate the specified dexamethasone dose in this study.
13. Prior autologous stem cell transplantation < 1 month or allogeneic stem cell transplantation < 4 months prior to C1D1.
14. Active graft versus host disease (after allogeneic stem cell transplantation) at C1D1.
15. Pregnant or breastfeeding females.
16. Body Surface Area < 1.4 m2 at baseline, calculated by the Dubois or Mosteller method.
17. Life expectancy of < 4 months.
18. Major surgery within 4 weeks prior to C1D1.

19. Active, unstable cardiovascular function:

    1. Symptomatic ischemia, or
    2. Uncontrolled clinically significant conduction abnormalities (e.g., patients with ventricular tachycardia on anti-arrhythmics are excluded; patients with first-degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), or
    3. Congestive heart failure of New York Heart Association Class ≥ 3 or known left ventricular ejection fraction < 40%, or
    4. Myocardial infarction within 3 months prior to C1D1.
20. Known active human immunodeficiency virus (HIV) infection or HIV seropositivity
21. Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus ribonucleic acid (RNA) or hepatitis B virus surface antigen.
22. Active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment.
23. Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent.
24. Contraindication to any of the required concomitant drugs or supportive treatments.
25. Patients unwilling or unable to comply with the protocol, including providing 24-hour urine samples for urine protein electrophoresis at the required time points.