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

Inclusion Criteria:

1. Informed Consent: Signed informed consent by the participant or legally authorized representative.
2. Age \& Performance Status:

   * Age ≥ 18 years
   * ECOG performance status ≤ 2
3. 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.
4. Measurable Disease: Tumor ≥1.5 cm on CT/PET scan or evidence of disease in blood, BM, GI, skin, or spleen.
5. Prior CAR T-cell Therapy: Allowed if ≥ 3 months since last treatment and CD19 CAR-T persistence \< 5% before leukapheresis.
6. 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.
7. Infectious Disease Screening: Seronegative for HIV, active HBV, active HCV (or undetectable viral load if positive).
8. Reproductive Considerations:

   * Negative pregnancy test for females of childbearing potential.
   * Use of effective contraception or abstinence through 3 months post-treatment.

Exclusion Criteria:

1. Prior Therapies \& Transplants:

   * Prior allogeneic SCT.
   * Autologous SCT \< 6 months before leukapheresis.
   * Concurrent systemic steroids or chronic immunosuppressant use.
2. Disease-Specific Exclusions:

   * Cardiac lymphoma involvement.
   * Need for urgent therapy due to tumor-related complications (e.g., bowel obstruction).
3. 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.
4. Pregnancy \& Breastfeeding: Females who are pregnant or nursing.
5. Other Considerations:

   * Investigator-determined safety concerns.
   * Potential noncompliance with study procedures.