Safety and Efficacy of Anti-BCMA-GPRC5D CAR-T Cells Therapy in the Treatment of r/r MM

Inclusion Criteria: 1. The patient or his/her guardian understands and voluntarily signs the informed consent, and is expected to complete the follow-up examination and treatment of the study procedure; 2. Age 18-75 years old, gender unlimited; 3. Diagnosed as Multiple Myeloma (MM) according to the international standard for multiple myeloma (IMWG); 4. The presence of measurable disease at screening meets one of the following criteria:Serum M-protein ≥ 1.0 g/dL or Urine M-protein ≥ 200 mg/24h or diagnosed as Light-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 at least include: one Proteasome Inhibitor (PI), one Immunomodulatory Drug (IMiD), and one 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 the end of the last therapy; 8. The patient has recovered from the toxicity of the prior treatment, i.e., CTCAE toxicity grade \< 2 (unless the abnormality is related to the tumor or is stable as judged by the investigator and has little impact on safety or efficacy); 9. ECOG score 1-2 points and the expected survival period ≥ 3 months; 10. Liver, kidney and cardiopulmonary functions meet the following requirements: 1. Total bilirubin ≤ 1.5×ULN, alanine aminotransferase (ALT) ≤ 3 × ULN and aspartate aminotransferase (AST) ≤ 3 × ULN; 2. Serum creatinine ≤ 1.5×ULN, or creatinine clearance ≥ 60 mL/min; 3. Hemoglobin (Hb) ≥ 50 g/L without prior blood transfusion within 7 days; 4. Baseline peripheral oxygen saturation \> 92%; 5. Corrected serum calcium ≤ 12.5 mg/dL (≤ 3.1 mmol/L) or free (ionized, ionic) calcium ≤ 6.5 mg/dL (≤ 1.6 mmol/L); 6. Left ventricular ejection fraction (LVEF) \> 45%, without confirmed pericardiac effusion and abnormal electrocardiography with clinical significance; 7. Without clinically significant pleural effusion; 11. Venous access could be established; without contraindications of apheresis. Exclusion Criteria: 1. Have been diagnosed with or treated for aggressive malignancies other than multiple myeloma; 2. Prior antitumor therapy (prior to blood collection for CAR-T preparation) : targeted therapy, epigenetic therapy, or investigational drug therapy within 14 days or at least 5 half-lives, whichever is shorter; 3. It is suspected that MM has involved the central nervous system or meninges and has been confirmed by MRI or CT, or there are other active central nervous system diseases; 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 is higher than the lower limit of detection of the research institution; HCV antibody positive; HIV antibody positive; CMV DNA titer is higher than the lower limit of detection of the research institution; EBV DNA titer is higher than the lower limit of detection of the research institution; 6. Patients have a severe allergic history; 7. Any unstable systemic disease: including but not limited to unstable angina, cerebrovascular accident or transient cerebral ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), congestive heart failure \[New York Heart Association (NYHA) classification ≥ grade III\]; 8. Systemic diseases judged by researchers to be unstable: including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment; 9. Patients with acute/chronic graft-versus-host disease (GVHD) or requiring immunosuppressive therapy for GVHD within 6 months prior to screening; 10. Active autoimmune or inflammatory diseases of the nervous system; 11. Patients develop oncology emergencies and need to be treated before screening or infusion; 12. Uncontrolled infections that need antibiotics treatment; 13. Exposure to hematopoietic growth factor of cells within 1-2 weeks before apheresis; 14. Exposure to Corticosteriods or immunosuppressive agents within 2 weeks before apheresis; 15. Patients receive a major surgical operation within 4 weeks before lymphodepletion or do not recover completely before the enrollment; or plan to receive a major surgical operation during the study period; 16. Live attenuated vaccine within 4 weeks before screening; 17. Persons with serious mental illness; 18. Alcoholics or persons with a history of drug abuse; 19. Pregnant or Lactating Women; Patients and his or her spouse have a fertility plan within two years after CAR-T cell infusion; 20. Any unsuitable to participate in this trial judged by the investigator.