Inclusion Criteria:
1. Age 18 to 80 years.
2. Newly diagnosed symptomatic multiple myeloma (NDMM) according to the International Myeloma Working Group (IMWG) criteria. Patients who have received up to 1 cycle of prior anti-myeloma therapy, excluding immunotherapeutic agents, are allowed to enroll.
3. Presence of measurable disease at diagnosis, meeting at least one of the following criteria:
A.Serum M-protein ≥ 1 g/dL (\> 10 g/L) measured by serum protein electrophoresis (SPEP) (for IgA or IgD myeloma, quantitative IgA or IgD levels may be used instead); OR
B.Urine M-protein ≥ 200 mg/24 hours; OR
C.If both serum and urine M-protein do not meet the above criteria, an abnormal serum free light chain (FLC) ratio (normal FLC ratio: 0.26 to 1.65) with an involved serum FLC level ≥ 100 mg/L.
4. Accompanied by myeloma-related renal impairment (RI), defined as an estimated glomerular filtration rate (eGFR) \< 40 mL/min (calculated using the Modification of Diet in Renal Disease \[MDRD\] formula). The type of renal impairment must be restricted to cast nephropathy, which can be confirmed by renal biopsy or by the investigator's clinical judgment based on light chain proteinuria. If urine albumin accounts for more than 30% of the total urine protein, a renal biopsy is mandatory to confirm cast nephropathy.
5. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2.
6. Adequate major organ function, meeting the following criteria:
A. Hematological function:
1. Absolute neutrophil count (ANC) ≥ 1.0 × 10\^9/L, and without receiving granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 7 days, or pegylated G-CSF within 14 days prior to testing;
2. Hemoglobin ≥ 60 g/L, and without receiving whole blood or red blood cell transfusions within 7 days prior to testing;
3. Platelet count ≥ 50 × 10\^9/L, and without receiving whole blood, platelet transfusions, or thrombopoietin receptor agonists (TPO-RAs) within 7 days prior to testing.
B. Hepatic function:
Alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≤ 3 × ULN, and total bilirubin ≤ 2 × ULN (subjects with a history of Gilbert's syndrome are eligible if direct bilirubin ≤ 2.0 × ULN).
C. Coagulation function:
7. International Normalized Ratio (INR) or Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN.
8. No active concomitant malignancies or malignancies with an expected survival of less than 12 months.
9. Willingness to participate in the study, good compliance, and ability to sign the informed consent form (ICF).
Exclusion Criteria:
1. Diagnosis of smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS), Waldenström's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, amyloidosis, or secondary plasma cell leukemia.
2. Central nervous system (CNS) involvement or clinical evidence of meningeal involvement.
3. Severe and/or uncontrolled cardiac diseases, including: unstable angina, symptomatic congestive heart failure, myocardial infarction within 6 months prior to enrollment, severe and uncontrolled arrhythmias; or other cardiovascular/cerebrovascular diseases deemed unsuitable for study participation by the investigator.
4. Presence of active infections, including: HIV positive; active Hepatitis B (HBV-DNA positive); active Hepatitis C (HCV-RNA positive); active or latent syphilis infection (Treponema pallidum antibody positive); active tuberculosis (active TB infection indicated by chest imaging or other relevant tests within the past 3 months or during the screening period); or other active infections deemed unsuitable for study participation by the investigator.
5. Patients with concurrent malignancies; or severe concomitant diseases that, in the investigator's judgment, would severely compromise patient safety or interfere with study completion.
6. Pregnant or lactating women.
7. History of severe allergic reactions (Grade ≥ 3) or hypersensitivity to any components of the study drugs.
8. Unable or unwilling to sign the informed consent form.
9. Any other conditions that, in the opinion of the investigator, make the patient unsuitable for enrollment.
