BCMA-GPRC5D CAR-T Cells for Multiple Myeloma

Inclusion Criteria: Patient or his or her legal guardian voluntarily participates in and signs an informed consent form; Aged ≥ 18 years and ≤ 75 years; Diagnosed as Multiple Myeloma (MM) according to the international standard for multiple myeloma (IMWG); 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; 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; diagnosed as relapsed/refractory disease or primary refractory disease; The last treatment is ineffective, or the disease progresses within 60 days after the end of the last therapy; Patients must recover from the toxicity of the last therapy (< grade 2 by CTCAE criteria); ECOG score 1-2 points and the expected survival period ≥ 3 months; Liver, kidney and cardiopulmonary functions meet the following requirements: Total bilirubin ≤ 1.5×ULN, alanine aminotransferase (ALT) ≤ 3 × ULN and aspartate aminotransferase (AST) ≤ 3 × ULN; Serum creatinine ≤ 1.5×ULN, or creatinine clearance ≥ 60 mL/min; Hemoglobin (Hb) ≥ 50 g/L without prior blood transfusion within 7 days; Baseline peripheral oxygen saturation > 92%; Corrected serum calcium ≤ 12.5 mg/dL (≤ 3.1 mmol/L) or free (ionized, ionic) calcium ≤ 6.5 mg/dL (≤ 1.6 mmol/L); Left ventricular ejection fraction (LVEF) > 45%, without confirmed pericardiac effusion and abnormal electrocardiography with clinical significance; Without clinically significant pleural effusion; Venous access could be established; without contraindications of apheresis. Exclusion Criteria: Previous diagnosis and treatment of other malignancies within 3 years; Patients received previous anti-tumor therapies before apheresis including following therapies: targeted therapies, epigenetics modulation drugs, other drugs or medical devices (invasive) of clinical trials, monoclonal antibodies, cytotoxic agents, PIs, IMiDs, radiotherapy; Central Nervous System (CNS) involvement; Patients with Fahrenheit macroglobulinemia, POEMS syndrome, or primary AL, amyloidosis; 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; Patients have a severe allergic history; Patiens have severe systemic diseases or poor cardiovascular, liver, kidney functions; Acute or chronic graft versus host disease (GvHD) occurs within 6 months before the screening or needs be treated with immunosuppressive agents; Active autoimmune or inflammatory diseases of the nervous system; Patients develop oncology emergencies and need to be treated before screening or infusion; Uncontrolled infections that need antibiotics treatment; Exposure to hematopoietic growth factor of cells within 1-2 weeks before apheresis; Exposure to Corticosteriods or immunosuppressive agents within 2 weeks before apheresis; 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; Live attenuated vaccine within 4 weeks before screening; Patients with severe mental illness; Patients are addcited to alcohol or drugs; Pregnant or Lactating Women; Patients and his or her spouse have a fertility plan within two years after CAR-T cell infusion; Other conditions considered inappropriate by the researcher.