Multiple Myeloma Clinical Trials

• The subject voluntarily signs the informed consent form, is willing and able to comply with all study requirements.

• Age 18-75 years, male or female.

• Diagnosis of active MM according to the diagnostic criteria established by the International Myeloma Working Group (IMWG).

• Must have undergone stem cell transplantation (SCT) or be transplant-ineligible.

• Must have received at least 2 prior lines of anti-MM therapy (including immunomodulatory drugs, proteasome inhibitors, and anti-Cluster of Differentiation 38 (CD38) therapy, as single agents or in combination. Patients who are intolerant or have contraindications to these therapies are eligible for enrollment if they meet other inclusion/exclusion criteria). Each line of therapy must have included at least one complete cycle, and there must be documented evidence of disease progression on or relapse after the last line of therapy, or permanent discontinuation of therapy due to treatment-related toxicities (the reason for permanent discontinuation due to toxicity must be documented in the CRF). Furthermore, the patient must be refractory or intolerant to any established standard-of-care regimen that, in the investigator's assessment, is of significant clinical benefit to the patient.

• The subject's tumor sample (bone marrow) tests positive for B-Cell Maturation Antigen (BCMA) expression on the plasma cell membrane via immunohistochemistry (IHC) or flow cytometry.

• Presence of measurable disease at screening determined by any one of the following criteria:

‣ Proportion of clonal plasma cells in bone marrow cytology, bone marrow biopsy histology, or flow cytometry ≥ 5%;

⁃ Serum monoclonal protein (M-protein) level: Immunoglobulin G (IgG) type M-protein ≥10 g/L; or Immunoglobulin A (IgA), Immunoglobulin D (IgD), Immunoglobulin E (IgE), Immunoglobulin M (IgM) type M-protein ≥5 g/L;

⁃ Urine M-protein level ≥200 mg/24 hours;

⁃ For MM without measurable serum or urine M-protein: involved serum free light chain ≥100 mg/L (10 mg/dL) and abnormal serum κ/λ free light chain ratio (\<0.26 or \>1.65);

⁃ Or clinical relapse: a. New bone lesions or soft tissue plasmacytomas (excluding osteoporotic fractures); b. Confirmed increase in Sum of the Product of Diameters (SPD) of existing plasmacytomas or bone lesions (≥50% increase in SPD of measurable lesions, absolute increase ≥1 cm).

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 (see Appendix 1 for ECOG scale).

• Expected survival time ≥12 weeks.

⁃ The subject must have adequate organ function, meeting all the following laboratory results prior to enrollment:

∙ Hematology: Absolute neutrophil count (ANC) ≥ 1×10\^9 /L (growth factor support is allowed, but must not have been administered within 7 days prior to the laboratory test); Absolute lymphocyte count (ALC) ≥0.3×10\^9 /L; Platelets ≥50×10\^9 /L (must not have received transfusion support within 7 days prior to the laboratory test); Hemoglobin ≥60 g/L (no red blood cell (RBC) transfusion within 7 days prior to the laboratory test; recombinant human erythropoietin is allowed);

‣ Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN); Serum total bilirubin ≤1.5 × ULN;

‣ Renal function: If available, measured CrCl from 24-hour urine collection; otherwise, calculated creatinine clearance (CrCl) via Cockcroft-Gault formula ≥ 40 ml/min;

‣ Coagulation: Fibrinogen ≥1.0 g/L; Activated partial thromboplastin time (aPTT) ≤1.5 × ULN; Prothrombin time (PT) ≤1.5 × ULN;

‣ Oxygen saturation \>91% (on room air);

‣ Left ventricular ejection fraction (LVEF) ≥ 50 %;

‣ No clinically significant pericardial effusion detected.

⁃ The subject and their spouse agree to use effective barrier or pharmacological contraception from signing the informed consent until one year after CAR-T cell infusion (excluding the rhythm method).