The following criteria is provided for health care professionals.

Inclusion Criteria:

1. Written informed consent in accordance with federal, local, and institutional guidelines.
2. Age ≥ 18 years at the time of informed consent.
3. Histologically confirmed diagnosis with measurable disease for relapsed/refractory myeloma.
4. Symptomatic MM for NDMM needing therapy, based on IMWG guidelines.
5. Patients must have measurable disease as defined by at least one of the following:
   1. Serum M-protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP) or, for IgA myeloma, by quantitative IgA
   2. Urinary M-protein excretion at least 200 mg/24 hours
   3. Serum FLC ≥ 100 mg/L, provided that FLC ratio is abnormal
   4. If SPEP is felt to be unreliable for routine M-protein measurement (e.g., for IgA MM), then quantitative Ig levels by nephelometry or turbidometry are acceptable
6. Any non-hematological toxicities (except for peripheral neuropathy as described in exclusion criterion #22) that patients had from treatments in previous clinical studies must have resolved to ≤ Grade 2 by Cycle 1 Day 1.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
8. Adequate hepatic function within 28 days prior to C1D1:
   • For SPd, SRd, and SPEd: Total bilirubin < 2x upper limit of normal (ULN) (except patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤ 3x ULN) and both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5x ULN
   • For SVd, SPVd, SDd, and SNd: Total bilirubin of < 1.5x ULN (except patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤ 3x ULN) and both AST and ALT < 2.0x ULN
   • For SKd: Total bilirubin < 2x ULN (except patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤ 3x ULN) and both AST and ALT < 3.0x ULN
9. Adequate renal function within 28 days prior to C1D1. Estimated creatinine clearance (CrCl) calculated using the formula of Cockroft and Gault (1976):
   • ≥ 20 mL/min for SVd, SDd, and SKd arms
   • ≥ 30 mL/min for SNd arm
   • ≥ 45 mL/min for SPd, SPVd, and SPEd arms
   • > 60 mL/min for SRd arm
10. Adequate hematopoietic function within 28 days prior to C1D1: total white blood cell (WBC) count ≥ 1,500/mm³, ANC ≥ 1,000/mm³, hemoglobin (Hb) ≥ 8.0 g/dL, and platelet count ≥ 150,000/mm³.
11. Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 1 week following the last dose of study treatment.

    SPd (Arm 1) Only:

12. Relapsed and refractory MM with:

    1. Documented evidence of progressive disease (PD) after achieving at least stable disease (SD) for ≥ 1 cycle during a previous MM regimen (i.e., relapsed MM)
    2. ≤ 25% response (i.e., patients never achieved ≥ MR) or PD during or within 60 days from the end of the most recent MM regimen (i.e., refractory MM)
    3. Previously undergone ≥ 2 cycles of lenalidomide and a PI (in separate therapeutic regimens [not for maintenance] or in combination)
    4. In the expansion arm at RP2D, patients must not be pomalidomide refractory

    SVd (Arm 2) Only:

13. Relapsed or refractory MM with:

    1. Documented evidence of relapse after ≥ 1 previous line of therapy
    2. Not refractory to bortezomib in their most recent line of therapy

    SRd in RRMM (Arm 3) Only:

14. Patients who received ≥ 1 prior therapeutic regimen (prior lenalidomide is allowed as long as patient's MM was not refractory to prior lenalidomide; patients whose MM was refractory to lenalidomide maintenance regimens will be allowed in this cohort).

    SPVd (Arm 4) Only:

15. Patients who received 1- 3 prior lines of therapy, including ≥ 2 cycles of lenalidomide and have demonstrated disease progression on their last therapy (may include prior bortezomib, as long as the patient's MM was not refractory to bortezomib therapy), but patients must be pomalidomide-naïve in the Dose Expansion at RP2D (Cohort 4.3 ONLY).

    SDd (Arm 5) Only:

16. Patients who received ≥ 3 prior lines of therapy, including a PI and an IMiD, or patients with MM refractory to both a PI and an IMiD.

17. Patients must not have received prior anti-CD38 monoclonal antibodies (Cohort 5.3 ONLY - Dose Expansion at RP2D).

    SKd (Arm 6) Only:

18. Patients may have received prior PIs; however, their MM must NOT be refractory to carfilzomib.

    SRd in NDMM (Arm 7) Only:

19. Patients must have symptomatic myeloma per IMWG guidelines with either CRAB criteria or myeloma-defining events and need systemic therapy. No prior systemic therapy for NDMM is permitted other than pulse dose dexamethasone (maximum dose of 160 mg) or corticosteroid equivalent.

    SNd (Arm 8) Only:

20. Patients must have MM that relapsed after 1 - 3 prior lines of therapy (may not include those with MM refractory to bortezomib or carfilzomib and patients must be ixazomib-naïve).

    SPEd (Arm 9) Only:

21. Patients who received ≥ 2 prior therapies, including lenalidomide and a PI (in separate or the same regimens), but patients must be pomalidomide-naïve and elotuzumab-naïve in the Dose Expansion at RP2D (Cohort 9.3 ONLY).

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not eligible to enroll in this study:

1. Smoldering MM
2. MM that does not express M-protein or FLC (i.e., non-secretory MM is excluded), and quantitative immunoglobulin levels cannot be used instead
3. Documented active systemic amyloid light chain amyloidosis
4. Active plasma cell leukemia
5. Red Blood Cell (RBC) and platelet transfusions and blood growth factors within 14 days of C1D1.
6. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks prior to C1D1, and radio-immunotherapy within 6 weeks prior to C1D1. Patients on long-term glucocorticoids during Screening do not require a washout period. Prior radiation is permitted for treatment of fractures or to prevent fractures as well as for pain management
7. Patients with history of SCC with residual paraplegia (Dose Escalation Phase only).
8. Treatment with an investigational anti-cancer therapy within 3 weeks prior to C1D1
9. Prior autologous stem cell transplantation < 1 month, or allogeneic stem cell transplantation < 3 months prior to C1D1
10. Active graft versus host disease after allogeneic stem cell transplantation
11. Life expectancy < 3 months
12. Major surgery within 4 weeks prior to C1D1
13. Active, unstable cardiovascular function:
    1. Symptomatic ischemia, or
    2. Uncontrolled clinically-significant conduction abnormalities (e.g., patients with ventricular tachycardia on antiarrhythmics are excluded; patients with 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or
    3. Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥ 3, or
    4. Myocardial infarction (MI) within 3 months prior to C1D1
    5. Ejection fraction (EF) < 50% at Screening
14. Uncontrolled active hypertension
15. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose
16. Known active hepatitis A, B or C
17. Known HIV infection or HIV seropositivity
18. Any active gastrointestinal dysfunction that prevents the patient from swallowing tablets or interferes with absorption of study treatment
19. Currently pregnant or breastfeeding
20. A serious psychiatric or medical condition which, in the opinion of the Investigator, could interfere with treatment
21. Hypersensitivity to any of the treatments for the Arm in which the patient is enrolled
22. Prior exposure to a SINE compound, including selinexor

    In the SVd Arm (Arm 2), SPVd (Arm 4), and SNd Arm (Arm 8) only:

23. Prior history of neuropathy Grade > 2, or Grade ≥ 2 neuropathy with pain at screening (within 28 days prior to C1D1).

    Patients who are eligible for the selinexor PK Run-in only:

24. Treatment with moderate or strong inhibitors/inducers of CYP3A within 7 days prior to Day 1 of the PK Run-in period

25. Not able to receive a strong CYP3A4 inhibitor due to concomitant medications

    SKd Arm only:

26. HBs Ag + plus HBc Ab + even though no active HBV hepatitis. If HBs Ag - plus HBc Ab +, treating physician needs to contact the medical monitor