Inclusion Criteria:
1. Age 18-75 years, any gender.
2. Diagnosis of multiple myeloma (MM) per International Myeloma Working Group (IMWG) diagnostic criteria.
3. Prior therapy requirements:
MM patients: ≥3 prior lines of therapy, including:
* 1 proteasome inhibitor (PI)
* 1 immunomodulatory drug (IMiD)
* 1 anti-CD38 monoclonal antibody Exception: No minimum line requirement for subjects refractory to PIs, IMiDs, and anti-CD38 therapy.
Primary plasma cell leukemia (pPCL): ≥1 prior line including ≥1 PI and ≥1 IMiD.
4. Documented disease progression during/within 12 months after last anti-myeloma therapy (exemption: No 12-month requirement if last line was CAR-T).
5. Measurable disease at screening (≥1 of the following):
Serum M-protein:
IgG ≥10 g/L IgA/IgD/IgE/IgM ≥5 g/L Urine M-protein ≥200 mg/24h Serum free light chains (FLC): Involved FLC ≥100 mg/L with abnormal κ/λ ratio Bone marrow plasma cells ≥30% (if no measurable M-protein/FLC).
6. ECOG performance status 0-1.
7. Life expectancy ≥12 weeks.
8. Adequate organ function (all lab values within 7 days prior to enrollment):
Hematology:
Absolute neutrophil count (ANC) ≥1×10⁹/L (allowed: growth factor support, but none within 7 days) Absolute lymphocyte count (ALC) ≥0.3×10⁹/L Platelets ≥50×10⁹/L (no transfusion within 7 days) Hemoglobin ≥60 g/L (no RBC transfusion within 7 days; erythropoietin allowed)
Liver:
ALT/AST ≤2.5×ULN Total bilirubin ≤1.5×ULN Renal: Calculated CrCl ≥40 mL/min (Cockcroft-Gault)
Coagulation:
Fibrinogen ≥1.0 g/L aPTT/PT ≤1.5×ULN Pulmonary: SpO₂ \>91% (room air) Cardiac: LVEF ≥50% (echocardiography).
9. Contraception: Subjects/partners must use effective contraception from consent through 1 year post CAR-T infusion (excluded: calendar method).
10. Signed informed consent approved by the Ethics Committee prior to screening.
Exclusion Criteria:
1. Active graft-versus-host disease (GVHD) or requiring long-term immunosuppressive therapy.
2. Prior hematopoietic stem cell transplantation (HSCT):
Autologous HSCT (Auto-HSCT) within 12 weeks before apheresis,
≥2 prior Auto-HSCTs, Any prior allogeneic HSCT (Allo-HSCT).
3. Prior cell therapy targeting plasma cells within 3 months before apheresis, or detectable residual cellular therapy products in peripheral blood.
4. Recent anti-myeloma therapies (relative to apheresis):
Monoclonal antibody treatment within 21 days, Cytotoxic chemotherapy or proteasome inhibitors within 14 days, Immunomodulatory drugs within 7 days, Other anti-tumor therapies within 14 days or 5 half-lives (whichever is shorter).
5. Chronic corticosteroid use (\>20 mg/day prednisone or equivalent), except for physiologic replacement, topical, or inhaled use.
6. Uncontrolled hypertension despite medication.
7. Severe cardiac disease, including:
Unstable angina, Myocardial infarction (within 6 months before screening), Congestive heart failure (NYHA Class ≥III), Severe arrhythmias.
8. Unstable systemic illnesses per investigator's judgment (e.g., severe hepatic, renal, or metabolic disorders requiring medication).
9. Other malignancies within 5 years, excluding:
Carcinoma in situ of the cervix, Basal/squamous cell skin cancer, Localized prostate cancer post-radical resection, Ductal breast carcinoma in situ post-resection.
10. History of solid organ transplantation.
11. Suspected or confirmed CNS involvement by plasma cell neoplasms.
12. Major surgery within 2 weeks before apheresis or planned within 2 weeks post-treatment (allowed: minor procedures under local anesthesia).
13. Investigational drugs within 1 month before apheresis.
14. Uncontrolled active infections:
Persistent symptoms despite appropriate therapy, Requiring IV antimicrobials at screening.
15. Viral infections:
HBV: HBsAg(+) or HBcAb(+) with detectable HBV DNA, HCV: HCV Ab(+) with detectable HCV RNA, HIV Ab(+), CMV DNA(+), Syphilis: TRUST(+) and TPPA(+).
16. Pregnancy or lactation.
17. Psychiatric disorders, cognitive impairment, or active CNS diseases.
18. Other conditions deemed ineligible by the investigator.
