BAFFR-targeting CAR T Cells for Patients With Relapsed or Refractory B-NHL

Inclusion Criteria

• Informed Consent: Signed informed consent by the participant or legally authorized representative.
• Age & Performance Status:
• Age ≥ 18 years
• ECOG performance status ≤ 2
• Diagnosis & Disease Criteria:
• Histologically confirmed B-NHL, including LBCL, MCL, and FL/MZL subtypes meeting specified prior treatment conditions.
• BAFF-R expression on lymphoma cells required.
• Measurable Disease: Tumor ≥1.5 cm on CT/PET scan or evidence of disease in blood, BM, GI, skin, or spleen.
• Prior CAR T-cell Therapy: Allowed if ≥ 3 months since last treatment and CD19 CAR-T persistence < 5% before leukapheresis.
• Organ Function & Laboratory Criteria:
• Hematologic: ANC ≥ 1000/μL, Platelets ≥ 75,000/μL (exceptions for BM involvement).
• Liver Function: Bilirubin ≤ 1.5x ULN (except Gilbert's), AST/ALT < 3x ULN.
• Renal Function: CrCl ≥ 50 mL/min.
• Cardiac & Pulmonary: LVEF ≥ 45%, QTcF ≤ 480 ms, O₂ saturation > 91% on room air.
• Infectious Disease Screening: Seronegative for HIV, active HBV, active HCV (or undetectable viral load if positive).
• Reproductive Considerations:
• Negative pregnancy test for females of childbearing potential.
• Use of effective contraception or abstinence through 3 months post-treatment.

Exclusion Criteria

• Prior Therapies & Transplants:
• Prior allogeneic SCT.
• Autologous SCT < 6 months before leukapheresis.
• Concurrent systemic steroids or chronic immunosuppressant use.
• Disease-Specific Exclusions:
• Cardiac lymphoma involvement.
• Need for urgent therapy due to tumor-related complications (e.g., bowel obstruction).
• Medical Conditions:
• Active autoimmune disease requiring immunosuppressants.
• Primary immunodeficiency.
• Cardiac conditions, including NYHA Class III/IV heart disease, arrhythmia, recent MI (≤ 6 months), stroke (≤ 6 months), or significant VTE (≤ 6 months).
• Neurologic conditions, including prior optic neuritis, CNS inflammatory diseases, or seizure disorders.
• History of malignancy, unless resected/treated with curative intent or in remission for ≥ 3 years.
• Uncontrolled systemic infections or active CNS lymphoma.
• Pregnancy & Breastfeeding: Females who are pregnant or nursing.
• Other Considerations:
• Investigator-determined safety concerns.
• Potential noncompliance with study procedures.