In Vivo BCMA/GPRC5D Tandem Dual CAR-T Therapy for Relapsed/Refractory Plasma Cell Neoplasms

Inclusion Criteria:

• Voluntary signing of informed consent by the subject or legally authorized representative, with willingness and ability to comply with scheduled visits, study treatment, laboratory tests, and other study procedures.

• Diagnosis of relapsed or refractory plasma cell neoplasms meeting the following criteria:

  1. Clonal plasma cells confirmed to be BCMA and/or GPRC5D positive by flow cytometry or immunohistochemistry;
  2. Previously treated with at least 2 lines of anti-plasma cell neoplasms therapy, with at least 1 complete treatment cycle for each line, and evidence of disease progression within 12 months after the most recent anti-plasma cell neoplasms treatment, or being refractory to both immunomodulatory drugs and proteasome inhibitors, with disease progression within 2 months after the most recent anti-plasma cell neoplasms treatment (according to the IMWG diagnostic criteria)
• Age 18 to 75 years (inclusive), male or female.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Life expectancy > 3 months from the date of informed consent.
• Hemoglobin (HGB) ≥ 60 g/L (transfusion allowed).

• Adequate organ function (hepatic, renal, cardiac, and pulmonary):

  1. Creatinine ≤ 2 × ULN;
  2. Left ventricular ejection fraction (LVEF) ≥ 50%;
  3. Oxygen saturation > 90%;
  4. Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN.
• Willingness to use highly effective contraception from signing of informed consent until 1 year after SL4903 infusion.

Exclusion Criteria:

• Severe cardiac dysfunction with left ventricular ejection fraction (LVEF) < 50%.
• History of severe pulmonary impairment.
• Concurrent diagnosis of another active malignancy.
• Uncontrolled active infection.
• History of severe autoimmune disease or primary immunodeficiency.
• Active hepatitis (defined as HBV DNA or HCV RNA above the lower limit of detection).
• Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), or active syphilis.
• History of severe hypersensitivity to biological products (including antibiotics).
• Allogeneic hematopoietic stem cell transplant recipients with ongoing acute graft-versus-host disease (GVHD) despite discontinuation of immunosuppressive therapy for at least one month prior to screening.
• Any other severe comorbidities or laboratory abnormalities that, in the investigator's opinion, would increase the risk to the subject or interfere with study results, rendering the subject unsuitable for participation.
• Pregnant or breastfeeding women (including women of childbearing potential who are pregnant or lactating).