Study of Selinexor Plus DRd for Newly Diagnosed Multiple Myeloma

Inclusion Criteria: 1. At least 18 years of age. 2. Have documented multiple myeloma as defined by the International Myeloma Working Group (IMWG) 2015 criteria below: Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma. \* In addition, the patient must meet one of the criteria in either 2a or 2b. 1. Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically at least one of the following: * i. Hypercalcemia: serum calcium \>0.25 mmol/L (\>1 mg/dL) higher than the upper limit of normal (ULN) or \>2.75 mmol/L (\>11 mg/dL) * ii. Renal insufficiency: creatinine clearance 20-40 mL per min or serum creatinine \>177 μmol/L (\>2 mg/dL) * iii. Anemia: hemoglobin value of \> 2 g/dL below the lower limit of normal, or a hemoglobin value \<10 g/dL\* * iv. Bone lesions: one or more osteolytic lesions on skeletal radiography, or CT (computed tomography) \*\*. 2. Any one or more of the following: * i. Clonal bone marrow plasma cell percentage\* ≥60% * ii. Involved: uninvolved serum free light chains (FLC) ratio\*\*\* \>100 * iii. \>1 focal lesions on MRI (magnetic resonance imaging) studies; Each focal lesion must be 5 mm or more in size. * Clonality should be established by showing κ/λ-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used. * If bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement. * These values are based on the serum Freelite assay. The involved FLC must be ≥100 mg/L. 3. Have measurable disease as defined by any of the following: 1. Serum M-protein level ≥0.5 g/dL or urine M protein level ≥200 mg/24 hours; or 2. Immunoglobulins A, D, E or M multiple myeloma: serum M-protein level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; or 3. Light chain multiple myeloma without measurable disease in the urine: serum Ig FLC ≥10 mg/dL and abnormal serum Ig kappa/lambda FLC ratio 4. Have previously untreated myeloma. For previously untreated patients an emergency course of steroids (defined as no greater than 40 mg of dexamethasone, or equivalent per day for a maximum of 4 days) is permitted. In addition, radiation therapy is permitted prior to study entry, during screening, and during study treatment as needed for lytic bone disease. 5. Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. 6. Female patients of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective methods of contraception throughout the study and for 90 days following the last dose of study treatment. Childbearing potential excludes: Age \>50 years and naturally amenorrhoeic for \>1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy. 7. Male patients who are sexually active must use highly effective methods of contraception throughout the study and for 3 months after receiving the last dose of study drug. Male patients must agree not to donate sperm during the study treatment period and for 3 months after receiving the last dose of study drug. 8. Patients must be willing and able to adhere to the prohibitions and restrictions specified in this protocol and referenced in the informed consent form (ICF). 9. Each patient (or their legally acceptable representative) must sign an ICF indicating that he or she understands the purpose of, and procedures required for the study and are willing to participate in the study. Exclusion Criteria: 1. Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma. 2. Is known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have a history of hepatitis C. Patients who completed treatment for hepatitis C and have no detectable circulating hepatitis C virus (HCV) by hepatitis C RNA polymerase chain reaction (PCR) for at least 6 months prior to screening, may participate in the study. Such patients will be required to undergo regular assessment for HCV reactivation during their participation in the study. Patients who test positive for HCV at any time during these assessments will be withdrawn from the study. 3. Has any concurrent medical condition or disease (e.g., active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study. 4. Has clinically significant cardiac disease, including: * Myocardial infarction (MI) within 6 months before first day of first cycle (C1D1), or unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV) * Uncontrolled cardiac arrhythmia (NCI-CTCAE Version 5.0 Grade 2 or higher) or clinically significant electrocardiogram (ECG) abnormalities 5. Screening 12-lead ECG shows a baseline QT interval (QTc) \>470 msec 6. Has any of the following laboratory test results during the screening phase: * Absolute neutrophil count ≤1.0 × 109 /L; (granulocyte colony stimulating factor use is permitted) * Hemoglobin level ≤7.5 g/dL (≤5 mmol/L); blood transfusions to maintain hemoglobin \>7.5 are acceptable * Platelet count \<75 × 109 /L for patients in whom \<50% of bone marrow nucleated cells are plasma cells; otherwise platelet count \<50 × 109 /L; no platelet transfusions in the past 7 days are allowed * Alanine aminotransferase (ALT) level ≥2.5 × upper limit of normal (ULN) * Aspartate aminotransferase (AST) level ≥2.5 × ULN * Total bilirubin level ≥1.5 × ULN, (except for Gilbert Syndrome: direct bilirubin 2 × ULN) * Creatinine clearance ≤20 mL/min estimated using Cockcroft-Gault; 7. Has known allergies, hypersensitivity, or intolerance to monoclonal antibodies or human proteins, daratumumab or its excipients (refer to Investigator's Brochure), or known sensitivity to mammalian-derived products 8. Has plasma cell leukemia (\>2.0 × 109 /L circulating plasma cells by standard differential), Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and/or skin changes), or amyloid light-chain amyloidosis 9. Is known or suspected of not being able to comply with the study protocol (e.g., because of alcoholism, drug dependency, or psychological disorder) or the patient has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (e.g., compromise their well-being) or that could prevent, limit, or confound the protocol-specified assessments 10. Is considering becoming pregnant 11. Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol- specified assessments 12. Has had major surgery within 2 weeks before C1D1, or will not have fully recovered from surgery, or has surgery planned during the time the patient is expected to participate in the study or within 2 weeks after the last dose of study drug administration. (Note: patients with planned surgical procedures to be conducted under local anesthesia may participate. Kyphoplasty is not considered a major surgery.) 13. Is eligible for stem cell transplant. Must be transplant ineligible as determined by their physician, or if transplant eligible, not expect to undergo transplant for at least 24 months after study enrollment. NOTE: Investigators should ensure that all study enrollment criteria have been met at screening. If a patient's status changes (including laboratory results or receipt of additional medical records) after screening but before C1D1 such that he or she no longer meets all eligibility criteria, then the patient should be excluded from participation in the study.