The purpose of this study is to evaluate the efficacy and safety of SVRd in NDMM patients presenting with extramedullary disease.

Study Design:

This protocol corresponds to a multicenter, open-label, single arm, exploratory study designed to determine the safety of the combination of selinexor combined with VRd in NDMM patients presenting with EMD. The patients who respond to this combination treatment will undergo allogeneic hematopoietic stem cell transplantation or no ASCT and followed by consolidation and maintenance treatment.

All patients will receive 4 courses of SVRd induction therapy, each cycle of treatment will compromise 4 weeks of Selinexor 60mg QW treatment. Transplantation could be performed after 2 courses of VRd consolidation therapy. If not receive transplantation will give 4 cycles of SVRd consolidation therapy. Maintenance treatment will continued for a maximum of 2 years.

Study design allows 35 patients. Induction treatment will consist of Selinexor 60 mg/day orally on d1,8,15,22, Bortezomib 1.3mg/m2 intravenously on d1,8,15,22, Lenalidomide 25 mg/d ( the dose will be adjusted according to creatinine clearance), orally on days 1 to14, Dexamethasone 20 mg/day orally on d1-2, d8-9,d15-16,d22-23

Inclusion Criteria:

1. Men and women aged with18-75 years old.
2. Confirmed diagnosis of Multiple Myeloma(MM) (IMWG consensus guidelines)
3. Newly diagnosed patients presenting with extramedullary disease (EMD) including solely paraskeletal plasmacytoma, plasmacytoma of soft tissue and other special sites detected by physical exam and confirmed by CT/MRI/PET-CT and/or biopsy (≥2cm).
4. ANC≥1.0*10^9/L, HGB≥75*10^9/L, PLT≥50*10^9/L (≥50% of bone marrow nucleated cells are plasma cells).
5. Patients whose expecting survival time will be more than 3 months.
6. Without active infectious disease.
7. Female patients of child-bearing potential must have a negative serum pregnancy test at screening and all patients agree to use two reliable methods of contraception for six months after their last dose of medication.
8. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
9. Each patient must sign an informed consent form (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. Patients who have HBV, HCV, and other acquired and congenital immunodeficiency diseases.
2. Patients who have grade 2 or higher of peripheral neuropathy or neuralgia according to the definition of NCI CTCAE version 4.0.
3. Plasma cell leukemia.
4. Serious thrombotic events.
5. Active, unstable cardiovascular dysfunction: a. symptomatic ischemia; b. Uncontrolled, clinically significant conduction abnormalities (except antiarrhythmic ventricular tachycardia), but patients with first-degree atrioventricular block or asymptomatic left anterior bundle/right fascicular block cannot be excluded. c. New York Heart Association (NYHA) Class III - IV or left ventricular ejection fraction (LVEF) <40%; d. Myocardial infarction Within 3 months before C1D1.
6. Significant hepatic dysfunction (ALT and AST ≥ 3 times the upper limit of normal (ULN)).
7. Serum bilirubin≥1.5 × ULN.
8. creatinine clearance <30 ml/min.
9. History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma.
10. Previous major operation within 30 days before C1D1.
11. Patients who have epilepsy, dementia requiring medication, or other mental disorders who are unable to understand or adhere to the study protocol.
12. According to the study protocol or in the opinion of the investigator,serious physical or mental illness that is likely to interfere with the study procedures/results.
13. Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
14. Current participation in another clinical trial.
15. Pregnant or lactating women.
16. Patients with other commodities that the investigators considered not suitable for the enrollment.