Clinical Study of the Safety and Efficacy of BCMA CAR-NK

Inclusion Criteria:

• Age 18 years or above, no gender preference.
• Patients who have received at least 3 prior lines of treatment for multiple myelomaand have failed at least proteasome inhibitor and immunomodulator therapy; Each linehas at least 1 complete treatment cycle unless the best remission status for thattreatment is documented as progressive disease (PD) (as per the IMWG efficacyevaluation criteria published in 2016, Appendix 4); PD must be documented during orwithin 12 months after receiving the last treatment.
• Presence of measurable lesions at screening, which are defined as any of the followingsituations: Serum M protein≥1 g/dL (≥10 g/L) Urinary M protein≥200 mg/24 hours Serum free light chain (FLC): abnormal serum FLC ratio (<0.26 or >1.65) and involved FLC≥10 mg/dL (100 mg/L)
• ECOG score (Appendix 1): 0~1.
• Expected survival≥3 months.
• The following test values within 7 days prior to lymphocyte clearance meet thefollowing criteria: Hematology Absolute lymphocyte count:≥0.5×109/L[Granulocyte colony-stimulating factor (G-CSF) is allowed, but subjects should not have received this supportive therapy within 7days prior to laboratory test during the screening period] Absolute neutrophilcount:≥1.0×10^9 /L[Granulocyte colony-stimulating factor (G-CSF) is allowed, but subjectsshould not have received this supportive therapy within 7 days prior to laboratory testduring the screening period]. Platelets:Subjects platelet count ≥50 x 10^9/L (subjects must not receive transfusionsupport within 7 days prior to laboratory test during the screening period) Hemoglobin:≥8.0g/dL (recombinant human erythropoietin is allowed) [subjects have not received a red bloodcell (RBC) transfusion within 7 days prior to laboratory test during the screening period]. Liver Total bilirubin (serum) :Total bilirubin (serum) ≤1.5 × ULN AST and ALT:≤3× ULN
• Peripheral venous pathway meets the requirements of intravenous drip.
• Subjects agree to use reliable methods for contraception from the time of signing theinformed consent till 1 year after the transfusion.
• Voluntary participation in the clinical trial and signing of the informed consentform.

Exclusion Criteria:

• Subjects who have had a severe anaphylactic reaction.
• Subjects who received the following anti-MM therapy within a specific time prior tolymphocyte clearance. Small molecule targeted therapy within 2 weeks or 5 half-lives (whichever is longer). Large-molecule drug within 4 weeks or 2 half-lives (whichever is longer). Cytotoxic drugs,modern Chinese medicine preparations with antitumor effects within 2 weeks. Immunomodulators therapy within 1 week.
• Subjects who have received a live or attenuated vaccine within 4 weeks prior tolymphocyte clearance.
• Subjects who have received the following therapy within 7 days prior to lymphocyteclearance, or that requires long-term treatment during the study period according tothe investigators: Systemic steroid therapy (except for inhaled one or topical use). Immunosuppressivetherapy. Treatment of graft-versus-host response.
• Subjects presenting with incomplete recovery or stabilization to grade 1 (NCI-CTCAEv5.0) of toxicity (including peripheral neuropathy) caused by prior treatments.
• Cardiac disease: episode of myocardial infarction≤6 months prior to lymphocyteclearance; episode of unstable angina, severe arrhythmia as judged by theinvestigators, or coronary artery bypass graft≤3 months prior to lymphocyte clearance.
• Women who are pregnant or breastfeeding.
• Subjects who, in the opinion of the investigators, have any clinical or laboratorytest abnormalities or other reasons that make them ineligible to participate in thisclinical study.