Inclusion Criteria:
1. Subjects fully understand and voluntarily participate in this study and sign the informed consent;
2. Age≥18, no gender limitation;
3. Active multiple myeloma patients with newly diagnosed by International Myeloma Working Group (IMWG) 2014 criteria;
4. Measurable lesion per at least one of the following criteria : Serum monoclonal protein ≥10 g/L; Urinary monoclonal protein ≥200 mg/24h; Serum free Light Chain (FLC) assay showed an involved FLC level ≥100 mg/L with abnormal ratio for FLC (κ/λ);
5. Radiographic \[X-ray, computer tomography (CT), magnetic resonance imaging (MRI), positons emission tomography coupled with a computer tomography (PET-CT)\] evidence of at least one lytic bone lesion;
6. Plan to receive primary frontline anti-myeloma therapies, or receiving less than one cycle of frontline anti-myeloma therapy (less than 30 days, does not include radiotherapy or a single short course of steroid), the treatment regimens were limited to VRd, D-VRd, DRd, and VCd;
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
8. Adequate organ function, as defined by the following criteria (per laboratory values):
1. Liver function: Serum total bilirubin ≤ 2.0 x upper limit of normal (ULN), Serum alanine aminotransferase ≤ (ALT) 2.0 x ULN, Serum aspartate aminotransferase (AST) ≤ 2.0 x ULN
2. Renal function: Serum creatinine clearance (CrCL) ≥ 30 mL/min, calculated by the Cockcroft-Gault formula
3. Serum calcium or albumin-adjusted serum calcium ≥2.0 mmol/L (8.0 mg/dL) and ≤ 2.9 mmol/L (11.5 mg/dL)
9. Reproductive potential subjects should be receiving effective contraception (Both male and female reproductive potential subjects, from the date of signing the informed consent to 6 months after the end of treatment);
10. Expected survival time ≥ 3 months;
Exclusion Criteria:
1. POEMS syndrome;
2. Plasma cell leukemia;
3. Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw; Non-healed dental/oral surgery, including tooth extraction; Active dental or jaw condition which requires oral surgery; Planned invasive dental procedures;
4. Planned radiation therapy or Orthopedic surgery;
5. Prior administration of denosumab or bisphosphonates;
6. Patients with active bone metabolic diseases (Paget disease of bone, Cushing syndrome and hyperprolactinemia), rheumatoid arthritis, uncontrolled hyper/hypothyroidism or hyper/hypoparathyroidism;
7. Uncontrolled concurrent diseases, including but not limited to: symptomatic congestive heart failure, hypertension (blood pressure remains \> 150/90 mmHg after standard therapy), unstable angina, arrhythmia requiring medication or instruments, history of myocardial infarction within 6 months, echocardiography showing left ventricular ejection fraction \<50%;
8. Active bacterial or fungal infections requiring systemic treatment within 7 days before randomization;
9. Known infection with human immunodeficiency virus (HIV), active infection with Hepatitis B virus (positive hepatitis B surface antigen and positive HBV-DNA) or Hepatitis C virus(positive hepatitis C surface antigen and positive HCV-RNA);
10. Pregnancy (serum β-HCG positive) or lactation;
11. Use of any of the following anti-bone metabolism drugs within 6 months before enrollment:
1. parathyroid hormonerelated peptides
2. calcitonin
3. osteoprotegerin
4. mithramycin
5. strontium ranelate
12. Known sensitivity to narlumosbart, denosumab, calcium or vitamin D;
13. Any other factors not suitable for participation in this study that in the opinion of the investigator.
