DVRd in the Treatment of Patients With Newly Diagnosed Double-hit Multiple Myeloma

Inclusion Criteria:

1. Voluntarily signing the Informed Consent Form (ICF).
2. Age: ≥ 18 years old and < 70 years old.
3. Newly diagnosed MM according to International Myeloma Working Group (IMWG) criteria,with at least one measurable disease: The serum M protein detected by serum proteinelectrophoresis (SPEP) is ≥ 1g/dL (≥ 10 g/L), or if it is immunoglobulin A (IgA) orimmunoglobulin D (IgD) subtype, quantitative levels of total IgA or IgD can be used asa substitute; Or urine M-protein level ≥ 200 mg/24 h; Or if only the serum free lightchain (FLC) ratio is abnormal, the affected serum FLC ≥ 100 mg/L (normal FLC ratio: 0.26 to 1.65).
4. At least two high-risk cytogenetic abnormalities: t(4;14), t(14;16), t(14;20),del(17p), gain/amp(1q) (the threshold for copy number variation is 20%, and thethreshold for translocation is 10%.
5. The Eastern Cooperative Oncology Group (ECOG) score is 0, 1, or 2 points. The ECOGscore of 3 points due to myeloma bone disease can be included.
6. Subjects had not received any anti-MM chemotherapy, extensive pelvic irradiation (morethan half of the pelvic area), or anti-MM glucocorticoids, except those who usedglucocorticoids for no more than 14 days to control symptoms.
7. Total bilirubin < 1.5 × upper limit of normal (ULN) (total bilirubin in patients withGilbert's syndrome can be restricted to <3 × ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.
8. Creatinine clearance rate ≥ 30 mL/min (calculated by cockcroft and Gault formulas).
9. Routine blood test within 7 days before the first day of cycle 1 meets the followingcriteria: white blood cell (WBC) count ≥ 1.5×10^9/L, absolute neutrophil count ≥ 1.0×10^9/L, hemoglobin ≥ 75 g/L, and platelet count ≥ 75×10^9/L (if bone marrowplasmacytes < 50%) or platelet count ≥ 50×10^9/L (if bone marrow plasmacytes ≥ 50%).
10. Patients receiving erythropoietin, granulocyte colony stimulating factor (G-CSF),granulocyte macrophage colony stimulating factor (GM-CSF), platelet agonists (forexample, eltrombopag, thrombopoietin, interleukin-11), must have a 2-week intervalbetween receiving growth factor support and screening assessment.
11. Patients receiving blood product transfusions: at least 2 weeks between hemoglobinassessment and the last red blood cell (RBC) transfusion; at least one week betweenplatelet assessment and the last platelet transfusion.
12. The subjects have no contraindications of receiving prophylactic anticoagulant drugrecommended by the study.
13. Female subjects of childbearing age must meet the following two criteria: agree totake effective contraceptive measures from the date of signing the ICF to 3 monthsafter the last administration of the drug; negative serum pregnancy test duringscreening.

Exclusion Criteria:

1. Primary plasma cell leukemia.
2. Secondary amyloidosis.
3. Central nervous system (CNS) involvement.
4. Patients planning to receive allogeneic hematopoietic stem cell transplantation.
5. Patients with > grade 2 peripheral neuropathy or ≥ grade 2 peripheral neuropathy withpain, regardless of receiving therapy or not.
6. Intolerance, allergy or contraindication to glucocorticoids, bortezomib, lenalidomideor daratumumab.
7. Clinically significant heart diseases: myocardial infarction before screening, orunstable or uncontrollable diseases related to or affecting cardiac function (such asunstable angina, congestive heart failure, New York Heart Association classificationIII-IV). Uncontrolled arrhythmia or clinically significant electrocardiogram (ECG)abnormalities. During screening, the 12-lead ECG showed a corrected QT interval (QTc)of > 470 msec.
8. Uncontrolled diabetes mellitus and hypertension.
9. Patients with a history of other malignant tumors within 5 years.
10. Active human immunodeficiency virus (HIV) infection or positive serum HIV.
11. Active hepatitis B or C infection. Hepatitis serological test should be performedduring screening. If hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) of patients are positive, DNA polymerase chain reaction (PCR) test should beconfirmed as negative before enrollment (After anti hepatitis B virus treatment, DNAPCR test should be confirmed as negative before enrollment). If hepatitis C antibodyis positive, RNA PCR test should be performed, and the results should be confirmed asnegative before enrollment.
12. Pregnant or lactating women.
13. Expected life < 6 months.
14. Any uncontrolled gastrointestinal dysfunction that affects the capacity to ingest orabsorb the tablets.
15. A major surgery history within 2 weeks prior to the start of screening, or will notfully recover from the surgery, or are scheduled for surgery during the study period.Kyphoplasty or vertebroplasty is not considered as a major surgery. Notes: Subjectswho plan to undergo surgery under local anesthesia can participate in the study.
16. Patients who received attenuated live vaccines within 4 weeks prior to the firstadministration of the study drug.
17. According to the researcher's judgment, any uncontrolled serious mental illness,physical illness, or other symptoms/conditions that may affect treatment, compliance,or the capacity to sign the ICF.
18. Patients with contraindications to any concomitant drugs or supportive therapy.
19. Patients with any diseases or complications that may interfere with the studyprocedure.
20. Patients who are unwilling or unable to follow the protocol.