BAFFR-targeting CAR T CellsBAFFR-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.