A Clinical Study to Evaluate the Safety and Efficacy of BCMA-GPRC5D CAR-T in Patients With Relapsed/Refractory Multiple Myeloma Who Received Three or More Lines of Therapy

Inclusion Criteria:

1. Patient or his or her legal guardian voluntarily participates in and signs an informedconsent form;
2. Aged ≥ 18 years and ≤ 75 years;
3. Diagnosed as Multiple Myeloma (MM) according to the international standard formultiple myeloma (IMWG);
4. The presence of measurable disease at screening meets one of the followingcriteria:Serum M-protein ≥ 1.0 g/dL or Urine M-protein ≥ 200 mg/24h or diagnosed asLight-chain MM without measurable disease in serum and urine; Serum free light chain ≥ 10 mg/dL with an abnormal κ/λ ratio;
5. Patients must relapse or be refractory after three or more lines of therapy, which atleast include: one Proteasome Inhibitor (PI), one Immunomodulatory Drug (IMiD), andone anti-CD38 monoclonal antibody;
6. diagnosed as relapsed/refractory disease or primary refractory disease;
7. The last treatment is ineffective, or the disease progresses within 60 days after theend of the last therapy;
8. Patients must recover from the toxicity of the last therapy (< grade 2 by CTCAEcriteria);
9. ECOG score 1-2 points and the expected survival period ≥ 3 months;
10. Liver, kidney and cardiopulmonary functions meet the following requirements:
11. Total bilirubin ≤ 1.5×ULN, alanine aminotransferase (ALT) ≤ 3 × ULN and aspartateaminotransferase (AST) ≤ 3 × ULN;
12. Serum creatinine ≤ 1.5×ULN, or creatinine clearance ≥ 60 mL/min;
13. Hemoglobin (Hb) ≥ 50 g/L without prior blood transfusion within 7 days;
14. Baseline peripheral oxygen saturation > 92%;
15. Corrected serum calcium ≤ 12.5 mg/dL (≤ 3.1 mmol/L) or free (ionized, ionic)calcium ≤ 6.5 mg/dL (≤ 1.6 mmol/L);
16. Left ventricular ejection fraction (LVEF) > 45%, without confirmed pericardiaceffusion and abnormal electrocardiography with clinical significance;
17. Without clinically significant pleural effusion;
18. Venous access could be established; without contraindications of apheresis.

Exclusion Criteria:

1. Previous diagnosis and treatment of other malignancies within 3 years;
2. Patients received previous anti-tumor therapies before apheresis including followingtherapies: targeted therapies, epigenetics modulation drugs, other drugs or medicaldevices (invasive) of clinical trials, monoclonal antibodies, cytotoxic agents, PIs,IMiDs, radiotherapy;
3. Central Nervous System (CNS) involvement;
4. Patients with Fahrenheit macroglobulinemia, POEMS syndrome, or primary AL,amyloidosis;
5. Subjects with positive HBsAg or HBcAb positive and peripheral blood HBV DNA titer ishigher than the lower limit of detection of the research institution; HCV antibodypositive; HIV antibody positive; CMV DNA titer is higher than the lower limit ofdetection of the research institution; EBV DNA titer is higher than the lower limit ofdetection of the research institution;
6. Patients have a severe allergic history;
7. Patiens have severe systemic diseases or poor cardiovascular, liver, kidney functions;
8. Acute or chronic graft versus host disease (GvHD) occurs within 6 months before thescreening or needs be treated with immunosuppressive agents;
9. Active autoimmune or inflammatory diseases of the nervous system;
10. Patients develop oncology emergencies and need to be treated before screening orinfusion;
11. Uncontrolled infections that need antibiotics treatment;
12. Exposure to hematopoietic growth factor of cells within 1-2 weeks before apheresis;
13. Exposure to Corticosteriods or immunosuppressive agents within 2 weeks beforeapheresis;
14. Patients receive a major surgical operation within 4 weeks before lymphodepletion ordo not recover completely before the enrollment; or plan to receive a major surgicaloperation during the study period;
15. Live attenuated vaccine within 4 weeks before screening;
16. Patients with severe mental illness;
17. Patients are addcited to alcohol or drugs;
18. Pregnant or Lactating Women; Patients and his or her spouse have a fertility planwithin two years after CAR-T cell infusion;
19. Other conditions considered inappropriate by the researcher.