Clinical Study on the Safety and Efficacy of BCMA-CART±ASCT in Treating Young Multiple Myeloma Patients

Clinical Study on the Safety and Efficacy of BCMA-CART±ASCT in Treating Young Multiple Myeloma Patients

Evaluate and compare the safety and efficacy of BCMA-CART ± ASCT in the treatment of newly diagnosed multiple myeloma (NDMM) in young patients

This study is a single-center, open-label, prospective investigator-initiated clinical study. Patients are assigned to treatment groups in a non-randomized manner based on their condition and disease status, and are divided into transplant and non-transplant groups according to whether ASCT is combined. The study analyzes and compares the safety and efficacy of BCMA-CART ± ASCT treatment in young MM patients.

Inclusion Criteria： Young female, 18-55 years old;

1. Subjects voluntarily participate in the study and sign the informed consent form (ICF) themselves or through their legal guardian;

2. Confirmed diagnosis of multiple myeloma through flow cytometry or immunohistochemistry;

3. Subjects must have adequate organ function and meet all of the following test results:

   • Serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN)
   • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
   • Creatinine clearance (CrCl) (Cockcroft-Gault formula) ≥ 40 ml/min
   • Prothrombin time (PT) ≤ 1.5 × ULN, activated partial thromboplastin time (APTT) < 1.5 × ULN, international normalized ratio (INR) < 1.5 × ULN
   • Hemoglobin (Hb) ≥ 60 g/L
   • Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L (no granulocyte colony-stimulating factor [G-CSF] or other growth factors received within 7 days prior to screening laboratory tests)
   • Absolute lymphocyte count (ALC) ≥ 0.5 × 10^9/L
   • Platelets (PLT) ≥ 50 × 10^9/L (no platelet transfusion received within 7 days prior to screening laboratory tests)
   • Left ventricular ejection fraction (LVEF) ≥ 45%
   • Blood oxygen saturation (SpO2) ≥ 92%

4. ECOG score of 0-1, see Appendix 5 for ECOG scoring;

5. Expected survival ≥ 3 months;

6. Female participants of childbearing potential must have a negative pregnancy test and not be breastfeeding; female or male participants of childbearing potential must use effective contraceptive methods or devices for 24 months after cell infusion.

Exclusion Criteria:

1. History of allergy to any component of the cellular product;

2. Severe heart disease, including but not limited to:

   • Myocardial infarction, coronary angioplasty, or stent implantation within 6 months prior to signing the ICF
   • Unstable angina
   • Severe arrhythmia
   • History of severe non-ischemic cardiomyopathy
   • Congestive heart failure (New York Heart Association [NYHA] class III or IV), NYHA scores are in Appendix 2

3. Stroke or seizure within 6 months prior to signing the ICF;

4. Autoimmune diseases, immunodeficiency, or other conditions requiring immunosuppressive therapy;

5. Malignant tumors other than multiple myeloma within 3 years prior to signing the ICF, except fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical surgery, ductal carcinoma in situ of the breast after radical surgery, and other in situ cancers at other sites one year after radical surgery, provided there is no ongoing treatment and no signs of recurrence during the screening period;

6. Presence of uncontrolled active infection;

7. Unstable systemic diseases as judged by the investigator, including but not limited to severe liver, kidney, or metabolic diseases requiring medication.

8. Within one week before lymphocyte collection, the storage device falls under any of the following conditions:

   • Peripheral blood hepatitis B virus (HBV) DNA test value is above the detection limit
   • Hepatitis C virus (HCV) antibody positive and peripheral HCV-RNA positive
   • Human immunodeficiency virus (HIV) antibody positive
   • Syphilis antigen or antibody positive
   • CMV-DNA positive

9. Within one week before lymphocyte collection, use of more than 5 mg/day of prednisone (or an equivalent dose of other corticosteroids);

10. Prior use of any CAR-T cell products or other genetically modified T cell therapies;

11. Prior BCMA-targeted therapy;

12. Vaccination with a live vaccine within 4 weeks before signing the ICF;

13. History of alcoholism, drug abuse, or psychiatric disorders; Other conditions that the investigator deems unsuitable for participation in this study.