CAR BCMA-70 CAR-T Cells for the Treatment of High-risk Plasma Cell Neoplasms

Clinical Study on the Safety and Efficacy of CAR BCMA-CD70 Dual-target CAR-T Therapy for High-risk Plasma Cell Neoplasms

This is a single arm study to evaluate the safety and efficacy of CAR BCMA-CD70 CAR-T cell therapy for high-risk plasma cell neoplasms.

Inclusion Criteria:

1. The subject or their legally acceptable representative has provided written informed consent and is willing and able to comply with all scheduled study visits, study treatment administration, laboratory tests, and other required trial procedures.

2. Clinically diagnosed with high-risk plasma cell neoplasm, meeting any one of the following molecular/cytogenetic or clinical criteria:

   1. Deletion of the short arm of chromosome 17 (del(17p)) with clonal proportion ≥ 20%, and/or TP53 gene mutation;
   2. IgH translocation (t(4;14), t(14;16), or t(14;20)) combined with 1q amplification (1q+) and/or deletion of the short arm of chromosome 1 (del(1p32));
   3. Chromosome 1 abnormalities: monoallelic del(1p32) plus 1q+, or biallelic del(1p32);
   4. β₂-microglobulin ≥ 5.5 mg/L with normal serum creatinine (< 1.2 mg/dL).

3. Age 18 to 75 years (inclusive), male or female.

4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.

5. Life expectancy > 3 months from the date of signed informed consent.

6. Hemoglobin (HGB) ≥ 60 g/L (transfusion permitted).

7. Adequate hepatic, renal, and cardiopulmonary function as defined by:

   1. Serum creatinine ≤ 2 × ULN;
   2. Left ventricular ejection fraction (LVEF%) ≥ 50%;
   3. Blood oxygen saturation > 90%;
   4. Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN.

8. Subject agrees to use highly effective contraception from the date of informed consent until 1 year after CAR-T cell infusion.

Exclusion Criteria:

1. Severe cardiac insufficiency with left ventricular ejection fraction (LVEF%) < 50%.
2. History of severe chronic lung disease associated with impaired pulmonary function.
3. Concurrent active or progressive malignant tumors other than the target plasma cell neoplasm.
4. Concurrent severe infection that cannot be effectively controlled with standard therapy.
5. Concurrent severe autoimmune disease or congenital immunodeficiency disorders.
6. Active viral hepatitis, defined as hepatitis B virus DNA (HBV-DNA) or hepatitis C virus RNA (HCV-RNA) levels above the lower limit of detection (LLOD).
7. Human immunodeficiency virus (HIV) infection, known acquired immunodeficiency syndrome (AIDS), or syphilis infection.
8. History of severe allergic reactions to biological products, including antibiotics.
9. Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with persistent acute graft-versus-host disease (aGVHD) that does not resolve within 1 month after discontinuing immunosuppressive therapy.
10. Presence of other severe physical or psychiatric illnesses, or significant laboratory abnormalities, that may increase the risks of study participation, interfere with study outcomes, or render the subject otherwise unsuitable for enrollment as determined by the investigator.
11. Female subjects of childbearing potential who are pregnant or breastfeeding.