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 informedconsent, and is expected to complete the follow-up examination and treatment of thestudy procedure;

2. Age 18-75 years old, gender unlimited;

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, whichat 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 afterthe end of the last therapy;

8. The patient has recovered from the toxicity of the prior treatment, i.e., CTCAEtoxicity grade < 2 (unless the abnormality is related to the tumor or is stable asjudged 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:

11. Total bilirubin ≤ 1.5×ULN, alanine aminotransferase (ALT) ≤ 3 × ULN andaspartate aminotransferase (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. Have been diagnosed with or treated for aggressive malignancies other than multiplemyeloma;

2. Prior antitumor therapy (prior to blood collection for CAR-T preparation) : targetedtherapy, epigenetic therapy, or investigational drug therapy within 14 days or atleast 5 half-lives, whichever is shorter;

3. It is suspected that MM has involved the central nervous system or meninges and hasbeen confirmed by MRI or CT, or there are other active central nervous systemdiseases;

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 limitof 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 beforescreening), myocardial infarction (within 6 months before screening), congestiveheart failure [New York Heart Association (NYHA) classification ≥ grade III];

8. Systemic diseases judged by researchers to be unstable: including but not limited tosevere liver, kidney or metabolic diseases requiring drug treatment;

9. Patients with acute/chronic graft-versus-host disease (GVHD) or requiringimmunosuppressive 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 orinfusion;

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 beforeapheresis;

15. 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;

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 planwithin two years after CAR-T cell infusion;

20. Any unsuitable to participate in this trial judged by the investigator.