Inclusion Criteria:
* Patients must meet all of the following inclusion criteria to be eligible to enroll in this study:
1. Willing and able to written informed consent (ICF) .
2. Age ≥ 18 years.
3. Newly diagnosed multiple myeloma as defined by IMWG(Rajkumar, Dimopoulos et al. 2014) , measurable disease as defined IMWG 2016 criteria(Table 5) (Kumar, Paiva et al.2016), and meet at least one of the following criteria:
1. Serum M-protein (SPEP) ≥ 5 g/L, If the MM type is IgA/IgD, that can be substituted by IgA/IgD quantitative level.
2. 24 hours-Urinary M-protein excretion ≥ 0.2 g (200 mg)
3. Serum FLC ≥ 100 mg/L with abnormal FLC ratio ( FLC Normal ratio:0.26 to 1.65)
4. According to mSMART 3.0 definition for high risk multiple myeloma:
1. High Risk genetic Abnormalities t(4;14) , t(14;16) , t(14;20) , Del 17p, p53 mutation, Gain 1q
2. R-ISS Stage 3
3. High Plasma Cell S-phase
4. GEP: High risk signature
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2. ECOG PS 3 allowed, if caused by myeloma.
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.
7. Adequate hepatic function: total bilirubin \< 1.5× upper limit of normal (ULN) (for patients with Gilbert's syndrome, a total bilirubin of \< 3× ULN is required), AST \< 2× ULN, and ALT \< 2× ULN.
8. Adequate renal function: estimated creatinine clearance ≥ 30 mL/min (calculated using the formula of Cockroft-Gault).
9. Adequate hematopoietic function within 7 days prior to C1D1 and met the following criteria: White blood cell (WBC) count ≥1.5×109/L, Absolute neutrophil count (ANC)≥1.0×109/L, Hemoglobin (HB) ≥85g/L and Platelet count (PLT) ≥75×109/L (patients whom \<50% of bone marrow nucleated cells are plasma cells) or PLT ≥ 50×109/L (patients whom ≥ 50% of bone marrow nucleated cells are plasma cells).
10. Patients could not receive hematopoietic growth factor treatment within 2 weeks prior to screening, These growth factors include Erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), Granulocyte macrophages-colony stimulating factor (GM-CSF), Platelet agonist, etc (Eltrombopag, Thrombopoietin (TPO), Interleukin-11).
11. Patients receive transfusions of blood products:
1. At least 2 weeks elapsed between the screening hemoglobin assessment and the last red blood cell infusion,
2. And at least 1 week elapsed between the screening platelet assessment and the last platelet infusion.
12. Patients must be able to take prophylactic anticoagulant therapy as recommended by the study.
13. Female patients of childbearing potential must meet below two criteria:
1. must agree to use effective contraception methods since signature in ICF, throughout the study and for 3 months following the last dose of study treatment.
2. must have a negative serum pregnancy test at screening. Note: A woman is considered of childbearing potential following menarche and until becoming postmenopausal (defined as no menstrual period for a minimum of 12 months) or permanently sterile (having undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy). A woman who is taking oral contraceptive or using intrauterine device is considered of childbearing potential.
Male patients (including those who have received vasectomy) must use a condom if sexually active with a female of child-bearing potential throughout the study and for 3 months following the last dose of study treatment.
Exclusion Criteria:
* Patients who meet any of the following criteria will not be enrolled:
1. Plasma cell leukemia.
2. Documented active amyloidosis.
3. Involvement of the central nervous system(CNS) by Multiple myeloma.
4. Prior exposure to a SINE compound, including ATG-010.
5. Currently, whether or not the patient is on medication, \> Grade 2 peripheral neuropathy or ≥ Grade ≥ 2 painful neuropathy at baseline.
6. Known intolerance, hypersensitivity, or contraindication to glucocorticoids, bortezomib, lenalidomide, and Selinexor (ATG-010) .
7. Active, unstable cardiovascular function, as indicated by the presence of:
1. Symptomatic ischemia, or
2. Uncontrolled clinically significant conduction abnormalities (eg, patients with ventricular tachycardia on anti-arrhythmics are excluded; patients with first degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), or
3. Congestive heart failure of New York Heart Association Class ≥3 or known left ventricular ejection fraction \<40%, or
4. Myocardial infarction within 6 months prior to C1D1.
8. Known positive serology for HIV or HIV seropositivity.
9. Known active hepatitis A, B, or C infection; eg. positive for HCV RNA or HBV-DNA.
10. Women who are pregnant or nursing.
11. Life expectancy of less than 6 months.
12. Any active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment.
13. Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent.
14. Contraindication to any of the required concomitant drugs or supportive treatments.
15. Has any concurrent diseases or complications that is likely to interfere with the study procedures.
16. Patients unwilling or unable to comply with the protocol.
