Selinexor for the Treatment of Intermediate and High-Risk Smoldering Multiple Myeloma

Inclusion Criteria:

* Age \>/= 18 years
* Histologically confirmed diagnosis of SMM according to the IMWG definition: serum M-protein \>/= 3 g/dL or BMPC \>10% but \<60%, or both.
* Should not meet CRAB criteria: hypercalcemia, anemia, bone lesions, or renal insufficiency thought to be related to the plasma cell disorder.
* Should have 1 of the following risk factors to be considered intermediate risk and 2 or more risk factors to be considered high-risk:
* BMPC\>/=20%
* M-spike \>/= 2g/dL
* Involved to uninvolved sFLC ratio of \>/= 20
* normal hepatic function within 28 days prior to C1D1
* Adequate renal function within 28 days prior to C1D1. Estimated creatinine clearance (CrCl) calculated using formula of Cockcroft and Gault. CrCl \>/= 15 mL/min.
* Adequate hematopoietic function within 28 days prior to C1D1: absolute neutrophil count (ANC)\>/=1.5 x10\^9/L, hemoglobin \>/=10g/dL, platelets \>/150x10\^9/L.
* Life expectancy of \>12 months.
* ECOG PS 0-1
* Subjects with reproductive potential must use 2 highly effective methods of effective contraception or practice sexual abstinence throughout the study and continue for 6 months after the study has closed. Subjects who are surgically sterile (e.g., history of bilateral tubal ligation, hysterectomy, or whos partner is sterile are not required to use additional modes of contraception.
* Ability to understand and willingness

Exclusion Criteria:

* Meets criteria for symptomatic MM as defined by any of the following, determined to be related to the plasma cell disorder

  * Hypercalcemia (corrected serum calcium \>11.0 mg/dL)
  * Renal insufficiency (creatinine \>2.0 mg/dL)
  * Anemia (hemoglobin \<10g/dL)
  * One or more osteolytic bone lesions on radiography, but more than one lesion required if \<10% clonal bone marrow plasma cells. Based on MRI imaging, there must be more than one lesion \>5mm in size.
  * Clonal bone marrow plasma cells ≥60%
  * An involved serum free light chain ≥ 100mg/L with the ratio of the involved/uninvolved free light chains also ≥100
* Documented systemic light chain amyloidosis
* Systemic corticosteroids \>10mg prednisone (or equivalent) daily for other medical conditions.
* Active invasive malignancy within the past 3 years that may affect the results or interfere with the interpretation of results of this study.
* Non-invasive malignancy that was not treated with curative intent within the past 3 years that may affect the results or interfere with the interpretation of the results of this study.
* Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 14 days of the receiving the first dose
* Known active HIV infection without adequate anti-retroviral therapy
* Active gastrointestinal dysfunction that prevents patient from swallowing tablets or may interfere with absorption of study treatment
* Pregnant, breast feeding, or planning to become pregnant within 6 months after the end of treatment.
* Subject of reproductive potential that is not willing to use two methods of highly effective contraception during treatment period and for 6 months after the end of treatment.
* Any major medical or psychiatric disorder that, in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results.
* Prior exposure to a SINE compound, including Selinexor.