Dual-target BCMA-GPRC5D CAR-T Cell Therapy for RR/MM With Extramedullary Infiltration

Inclusion criteria

• Voluntarily participate in the trial and have good compliance.
• Aged between 18 and 75 years old, regardless of gender.
• Diagnosed with relapsed or refractory multiple myeloma according to the criteria of the International Myeloma Working Group (IMWG)2, and have measurable extramedullary lesions due to multiple myeloma.
• Positive for BCMA and GPRC5D in flow cytometry of bone marrow or cerebrospinal fluid tumor cells or immunohistochemistry of tumor tissue.
• Organ functions: ① Cardiac function: Left ventricular ejection fraction > 50% (by echocardiogram) in the past 2 weeks. ② Liver function: Alanine aminotransferase and aspartate aminotransferase < 3 times the upper limit of normal (ULN). ③ Renal function: Creatinine clearance rate ≥ 40 mL/min (by Cockcroft and Gault formula). ④ Coagulation function: PT and APPT < 1.5 times the ULN. ⑤ Arterial oxygen saturation (SpO₂) > 95%. ⑥ Pulmonary function: FEV₁% predicted value ≥ 50%.
• Female patients of childbearing age must have a negative serum pregnancy test at screening and before receiving cyclophosphamide and fludarabine or melphalan treatment; male patients should be willing to use effective contraceptive methods for 1 year after receiving the study treatment.
• ECOG score ≤ 2.
• Expected survival time > 3 months.

Exclusion criteria

• Pregnant or lactating women.
• Active infections that have not been effectively controlled.
• Active autoimmune diseases that have not been effectively controlled.
• Adverse reactions caused by previous treatments have not recovered to CTCAE grade ≤ 1.
• For allogeneic transplant patients, active graft - versus - host disease (GVHD) that has not been effectively controlled.
• Presence of any of the following: HBV - DNA copy number above the lower limit of detection; positive hepatitis C antibody (HCV - Ab) with HCV - RNA copy number above the lower limit of measurability; positive anti - Treponema pallidum antibody (TP - Ab); positive human immunodeficiency virus (HIV) antibody test.
• Allergic or intolerant to fludarabine or cyclophosphamide.
• Suffering from known symptomatic non - plasma cell infiltrative central nervous system diseases.
• Uncontrollable cardiovascular and cerebrovascular diseases within 6 months, such as: a. New York Heart Association (NYHA) class III or IV congestive heart failure. b. Myocardial infarction occurred or coronary artery bypass grafting (CABG) was received ≤ 6 months before enrollment. c. Clinically significant ventricular arrhythmia or a history of unexplained syncope (excluding cases caused by vasovagal or dehydration). d. A history of severe non - ischemic cardiomyopathy.
• A history of other untreated malignancies within the past 5 years or having other untreated malignancies concurrently.
• The investigator assesses that the subject cannot or is unwilling to comply with the requirements of the study protocol.
• Previous use of a CAR - T vector with the same structure.