Selinexor With Alternating Bortezomib or Lenalidomide Plus Dexamethasone in TIE Newly Diagnosed MM Patients

Inclusion criteria

Inclusion Criteria: Patients must meet all of the following inclusion criteria to be eligible to enroll in this study: 1. Age \> 18 years 2. Willing and able to provide written informed consent in accordance with national, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure 3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of ≤ 2. ECOG 3 allowed if caused by myeloma 4. Newly diagnosed multiple myeloma with treatment demanding disease as defined by IMWG (Rajkumar, Dimopoulos et al. 2014) and measurable disease as defined IMWG 2016 criteria (Table 5) (Kumar, Paiva et al. 2016) 5. By treating physician considered in-eligible for high-dose therapy with stem-cell transplant 6. Patients must have received no prior chemotherapy for multiple myeloma. Patients must have received no prior radiotherapy to a large area of the pelvis (more than half of the pelvis). Patients must have received no prior steroid treatment for myeloma with the exception of a maximum of 14 days of treatment for symptom control (including dexamethasone 40mg). 7. Adequate hepatic function within 7 days prior to C1D1: 1. Total bilirubin \< 1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of \< 3 × ULN), and 2. Alanine aminotransferase (ALT) normal to \<2 × ULN. 8. Adequate renal function within 7 days prior to C1D1 as determined by estimated GFR of ≥ 30 mL/min, calculated using standard formula. 1. Adequate hematopoietic function within 7 days prior to C1D1: Absolute neutrophil count ≥1000/mm3, and platelet count ≥100,000/mm3 (patients for whom \<50% of bone marrow nucleated cells are plasma cells). If cytopenias are due a plasma cell infiltration in the bone marrow (biopsy-proven heavy-marrow involvement, as defined by having at least 30% marrow cellularity, with \> 50% of the cells being malignant plasma cells (documented marrow results required)); in this case, although there are no required lower limits of normal for the blood counts, the treating physician must use his/her medical judgment as to the appropriateness of this study therapy for these patients. 2. Erythropoietin-analogues are allowed. 3. Patients must have: * At least a 1-week interval from the last platelet transfusion prior to the screening platelet assessment. However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study. 9. 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 3 months following the last dose of study treatment. 10. Patients must be able to take prophylactic anticoagulation as recommended by study 11. Patients with pathologic fractures, infection at diagnosis or symptomatic hyperviscosity must have these conditions attended to prior to registration (i.e., intramedullary rod, I.V. antibiotics, plasmapheresis)