Clinical Study of BCMA-Targeted CAR T-Cell Injection in the Treatment of Patients With Relapsed/Refractory Multiple Myeloma

Exclusion Criteria

• •1. Subjects with a known history of allergy, hypersensitivity, intolerance, or contraindication to any component of CART-BCMA or drugs that may be used in the study (including fludarabine, cyclophosphamide, tocilizumab); or subjects allergic to beta-lactam antibiotics; or subjects with a history of severe allergic reactions.
• •2. Subjects who have previously received any CAR-T therapy or BCMA-targeted therapy.
• •3. Subjects who have received the following anti-multiple myeloma (anti-MM) treatments within the specified time frame before apheresis:
• •* Small-molecule targeted therapy within 4 weeks or five half-lives, whichever was longer
• •* Macromolecular drug therapy within 4 weeks or 2 half-lives (whichever is longer)
• •* Cytotoxic therapy or proteasome inhibitor within 2 weeks
• •* Immunomodulatory drug therapy within 1 week
• •* Radiotherapy within 1 week
• •4. Subjects who have received any investigational drug within 4 weeks prior to apheresis or are concurrently participating in another clinical study (except for the following: subjects participating in observational, non-interventional clinical studies, or those in the follow-up period of an interventional clinical study).
• •5. Patients who have received autologous hematopoietic stem cell transplantation (ASCT) within 12 weeks prior to apheresis or have previously received allogeneic stem cell transplantation (with no time limit).
• •6. Subjects who have received live vaccines or attenuated vaccines within 4 weeks prior to CART-BCMA apheresis.
• •Note: Administration of inactivated viral vaccines for seasonal influenza via injection is permitted; however, intranasal attenuated live influenza vaccines are not permitted.
• •7. Subjects who have received any of the following treatments within 7 days prior to apheresis, or are judged by the investigator to require long-term receipt of such treatments during the study:
• •* Cumulative corticosteroids use equivalent to ≥ 70 mg prednisone within 7 days prior to apheresis, or long-term receipt of therapeutic-dose corticosteroids during the study as judged by the investigator
• •* Immunosuppressive therapy
• •* Graft-versus-host disease therapy
• •* Central nervous system (CNS) prophylactic therapy
• •8. Toxicities resulting from previous treatments (including peripheral neuropathy) have not fully resolved or stabilized to Grade 1 (per NCI-CTCAE v5.0), except for those judged by the investigator to not affect the patient's safe receipt of treatment (e.g., alopecia).
• •9. Any clinically significant past or current history of CNS disorders, such as altered mental status, psychosis, dementia, neurocognitive, neurodegenerative, or neuroinflammatory diseases (e.g., Alzheimer's disease, Parkinson's disease, multiple sclerosis), epilepsy, seizures, hemiplegia, aphasia, stroke, subarachnoid hemorrhage or other CNS hemorrhage, and severe traumatic brain injury. For subjects with history of such CNS alterations, they must have fully recovered at least 1 year before administration.
• •10. Presence of meningeal, brainstem, spinal cord metastasis and/or compression, or active CNS metastasis; or suspected involvement of the CNS or meninges by multiple myeloma (MM), confirmed by magnetic resonance imaging (MRI) or computed tomography (CT).
• •11. Suspected involvement of the CNS or meninges by MM (confirmed by MRI or CT), or presence of other active CNS diseases.
• •12. Patients with plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes), or amyloidosis at screening.
• •13. Cardiac diseases: Current heart failure (New York Heart Association \[NYHA\] classification ≥ Class II, Appendix 2); severe cardiac diseases as determined by the investigator; myocardial infarction occurring ≤ 6 months before apheresis; unstable angina pectoris, severe arrhythmia (as judged by the investigator), or coronary artery bypass grafting (CABG) performed ≤ 3 months before apheresis.
• •14. Poorly controlled hypertension (systolic blood pressure \> 160 mmHg and/or diastolic blood pressure \> 100 mmHg), or a history of hypertensive crisis or hypertensive encephalopathy.
• •15. Patients who have undergone major surgery (other than diagnostic procedures or biopsies) or plasmapheresis within 4 weeks before apheresis or are expected to undergo major surgery during the study. Note: Patients scheduled for surgical procedures under local anesthesia may participate in the study. Kyphoplasty or vertebroplasty is not considered major surgery.
• •16. Subjects currently receiving thrombolytic, anticoagulant, or antiplatelet therapy.
• •17. Subjects with infections requiring intravenous antibiotic administration or hospitalization.
• •18. Subjects with active hepatitis B; subjects positive for hepatitis C virus (HCV) antibody and positive for HCV RNA; subjects positive for human immunodeficiency virus (HIV) antibody; subjects positive for syphilis screening antibody;
• •a) Non-active/asymptomatic carrier, chronic, or active HBV-infected subjects may be enrolled if they meet the following criteria: HBV deoxyribonucleic acid (DNA) \< 500 IU/mL (or 2500 copies/mL) at screening.
• •19. Pregnant or lactating women.
• •20. Subjects diagnosed with or treated for other invasive malignant tumors except multiple myeloma, except for the following cases: non-melanoma skin cancer that has been surgically removed, cured cervical carcinoma in situ, localized prostate cancer, low-stage bladder cancer, ductal carcinoma in situ of the breast, or malignant tumors with no recurrence and no treatment within 2 years before enrollment.
• •21. Subjects deemed by the investigator to be unsuitable for participation in this clinical study due to any clinical or laboratory abnormalities or other reasons.