Clinical Study to Evaluate the Safety and Efficacy of CAR-T in the Treatment of Relapsed or Refractory Multiple Myeloma

Prior treatment

• 2. Prior treatment with the following anti-cancer therapies (before leukapheresis for CAR-T cell production): received targeted therapy, epigenetic therapy, or investigational drug treatment within 14 days or at least 5 half-lives (whichever is shorter); received monoclonal antibody therapy within 21 days; received proteasome inhibitor therapy within 14 days; received immunomodulatory drug therapy within 7 days; received radiation therapy within 14 days (excluding bone marrow radiation ≤5% of bone marrow reserve).
• 3. Underwent hematopoietic stem cell transplantation within 2 months prior to screening.
• 9. Severe cardiac diseases, including but not limited to severe arrhythmias, unstable angina, extensive myocardial infarction, New York Heart Association class III or IV heart failure, myocardial infarction within ≤6 months prior to screening, coronary artery bypass grafting (CABG) performed, except for non-vascular vagal syncope or dehydration, severe non-ischemic cardiomyopathy, and resistant hypertension.
• 11. Had acute or chronic graft-versus-host disease (GVHD) within 6 months prior to screening or required immunosuppressive treatment for GVHD.
• 16. Receiving steroids or immunosuppressive drugs within 2 weeks of screening for planned CAR-T cell production:
  • a) Steroids: Received systemic corticosteroid treatment within 2 weeks of screening and judged by the investigator to require long-term systemic corticosteroid treatment (excluding inhalation or topical use); and received systemic corticosteroid treatment within 72 hours before cell infusion (excluding inhalation or topical use).
  • b) Immunosuppressive drugs: Receiving immunosuppressive drugs within 2 weeks of screening.
• 17. Underwent major surgery (excluding diagnostic surgery and biopsy) within 4 weeks prior to screening or has unhealed surgical wounds before enrollment.
• 18. Received (attenuated) live virus vaccines within 4 weeks before screening.

Other illness

• 1. Diagnosis or treatment of invasive malignancies other than multiple myeloma within 3 years, unless the malignancy has been curatively treated and there is no known active disease within 3 years before enrollment, or unless the patient has been fully treated for non-melanoma skin cancer with no evidence of disease.
• 4. History of central nervous system disorders.
• 6. Diagnosed with Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), or primary AL amyloidosis.
• 7. Positive for hepatitis B surface antigen (HBsAg) or positive for hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA quantification, positive for hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, cytomegalovirus (CMV) DNA, syphilis test, or Epstein-Barr virus DNA.
• 8. History of severe allergies (defined as Grade 2 or higher reactions) or known hypersensitivity to any active ingredients, excipients, mouse-derived products, or heterologous proteins included in this trial, including the conditioning regimen.
• 10. Unstable systemic diseases, as judged by the investigator, including but not limited to severe liver, kidney, or metabolic diseases requiring drug treatment.
• 12. Active autoimmune or inflammatory neurological diseases (e.g., Guillain-Barré syndrome, amyotrophic lateral sclerosis) and clinically significant active cerebrovascular diseases (e.g., cerebral edema, posterior reversible encephalopathy syndrome) at screening.
• 13. Requires emergency treatment for tumor emergencies at screening (e.g., spinal cord compression, intestinal obstruction, leukostasis, tumor lysis syndrome).
• 14. Has uncontrollable bacterial, fungal, viral, or other infections requiring antibiotic treatment.
• 19. Has severe mental illness.
• 20. History of alcohol abuse or substance abuse.
• 22. Patients who have contraindications to any study procedure or have other medical conditions that may place them at unacceptable risk according to the investigator 's judgment and/or clinical criteria.

Lab values

• 15. Received blood transfusions or hematopoietic cytokine drugs affecting the patient's blood counts within 2 weeks prior to screening for planned CAR-T cell production, as determined by the investigator to affect cell preparation.

Other

• 5. Clinical signs of active central nervous system (CNS) involvement or manifestations of multiple myeloma meningeal involvement.
• 21. Pregnant or lactating women and participants planning to become pregnant within 2 years after cell infusion or their partners planning to become pregnant within 2 years after cell infusion.

• 1. Patients or their guardians understand and voluntarily sign an informed consent form and are expected to complete the follow-up examinations and treatments related to the study.
• 2. Aged 18-75 years, any gender.
• 3. Diagnosed with multiple myeloma according to IMWG diagnostic criteria.
• 4. Documented evidence that the patient's multiple myeloma is refractory or relapsed, defined as:
  • a) Refractory: No response to salvage therapy (no response defined as no achievement of minimal response [MR] or disease progression during treatment), or disease progression within 60 days of the last treatment, or patients who achieved MR or higher but experienced disease progression.
  • b) Relapsed: No response to any treatment, including no achievement of MR or higher in any prior treatment, but with minimal changes in M-protein without clinical progression or relapse as per the progression definition.
• 5. Measurable disease at screening based on any of the following criteria: serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours, or diagnosed with light-chain multiple myeloma in the absence of measurable disease in serum or urine: serum immunoglobulin free light chain ≥10 mg/dL and an abnormal κ/γ free light chain ratio, extramedullary measurable lesions, or presence of tumor cells in bone marrow biopsy.
• 6. Patients have recovered from toxicity of prior treatment, with CTCAE toxicity grade ≤2 (unless the abnormality is related to the tumor or is deemed stable by the investigator with no significant impact on safety or efficacy).
• 7. ECOG performance status score of 0-2 and an expected survival of more than 3 months.
• 8. Adequate organ function, including:
  • ALT (alanine transaminase) ≤3 times the upper limit of normal (ULN).
  • AST (aspartate transaminase) ≤3 times ULN.
  • Total bilirubin ≤1.5 times ULN.
  • Serum creatinine ≤1.5 times ULN or creatinine clearance ≥30 mL/min (calculated by Cockcroft-Gault formula).
  • Oxygen saturation ≥92%.
  • Left ventricular ejection fraction (LVEF) ≥45%, confirmed by echocardiography with no evidence of pericardial effusion and no clinically significant electrocardiographic findings.
  • No clinically significant pleural effusion.
• 9. Establishing a required venous access for collection without any leukapheresis contraindications.