This study consists of two sequential treatment phases. In the first phase, patients with r/r aggressive B-NHL receive two cycles of glofitamab ± investigator-selected agents. In the second phase, patients eligible for CAR-T monotherapy undergo FC lymphodepletion followed by CAR-T infusion (2-4×10⁶/kg), while those eligible for CAR-T+ASCT receive conditioning chemotherapy with PBSC reinfusion on day 0 and CAR-T administration (2-4×10⁶/kg) on day +3 (±1). Patients demonstrating Deauville 4-5 or ctDNA positivity at day 28 post-CAR-T infusion subsequently receive four cycles of glofitamab consolidation therapy.

The study comprises two sequential treatment phases. In the first phase, eligible patients with r/r aggressive B-NHL receive 2 cycles of glofitamab ± X regimen (where X includes but is not limited to chemotherapy, antibody-drug conjugates, or small-molecule targeted agents, selected at the investigator's discretion). Peripheral blood lymphocyte apheresis is performed prior to initial glofitamab administration unless clinically contraindicated, with hematopoietic stem cell mobilization and collection timed per investigator assessment to achieve minimum required yields of ≥3×10⁸/kg mononuclear cells and ≥2×10⁶/kg CD34+ cells.

Patients successfully completing phase 1 proceed to phase 2 treatment. In the CAR-T alone cohort, patients receive FC lymphodepleting therapy (days -5 to -3) followed by CAR-T cell infusion (2-4×10⁶/kg) on day 0. The CAR-T+ASCT cohort undergoes conditioning chemotherapy (regimen determined by investigator) with autologous PBSC reinfusion on day 0 and CAR-T cells (2-4×10⁶/kg) administered on day +3 (±1 day).

At day 28 post-CAR-T infusion, patients demonstrating PET-CT Deauville scores of 4-5 or ctDNA positivity initiate 4 cycles of glofitamab consolidation therapy.

Inclusion Criteria:

1. Patients with relapsed/refractory aggressive B-cell lymphoma, including the following subtypes: diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL), or transformed large B-cell lymphoma.

2. Relapsed or refractory disease, meeting criteria for one of the following cohorts:

   Cohort 1 (Relapsed/Refractory Disease):

   1. ≥2 prior lines of therapy (including both anti-CD20 monoclonal antibody and anthracycline-based chemotherapy) with documented progression following last treatment; OR

   2. Failure of first-line immunochemotherapy (containing anti-CD20 antibody and anthracycline) defined by any of:

      • Relapse/progression within 12 months of treatment completion; OR
      • Progressive disease during first-line therapy; OR
      • Stable disease as best response after 4 cycles; OR
      • Partial response as best response after 6 cycles.

   Cohort 2 (Early Treatment Failure):

   • Persistent metabolic activity (Deauville 5) on PET-CT after 2 cycles of first-line immunochemotherapy; OR
   • Biopsy-proven residual disease following initial therapy.

3. Age ≥18 years and ≤65 years.

4. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.

5. Hematologic parameters at screening must meet the following (unless due to bone marrow involvement):

   • Absolute neutrophil count (ANC) ≥1×10⁹/L,
   • Platelet count (PLT) ≥75×10⁹/L.

6. Biochemical parameters at screening must meet the following:

   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3× upper limit of normal (ULN);
   • Total bilirubin (TBIL) ≤1.5×ULN (unless due to Gilbert's syndrome or non-hepatic causes);
   • Serum creatinine (Cr) ≤2×ULN OR creatinine clearance ≥40 mL/min.

7. Left ventricular ejection fraction (LVEF) within institutional normal range by echocardiography.

8. Baseline oxygen saturation >92% on room air.

9. Life expectancy ≥3 months as assessed by the investigator.

Exclusion Criteria:

1. Confirmed primary central nervous system lymphoma;

2. Prior autologous or allogeneic hematopoietic stem cell transplantation;

3. Active HBV or HCV infection, defined as HBV-DNA or HCV-RNA levels above the upper limit of detection.

4. Uncontrolled comorbidities include infectious diseases, cardiovascular/cerebrovascular disorders, coagulopathies, and connective tissue diseases.

5. History of epilepsy or other central nervous system disorders;

6. Pregnancy or lactation;

7. HIV infection;

8. History of other malignancies unless:

   1. Disease-free for ≥5 years, or

   2. Previously cured of the following:

      • Non-melanoma skin cancers (basal cell carcinoma, squamous cell carcinoma, or related localized cutaneous malignancies)
      • Carcinoma in situ of cervix

9. Other conditions deemed ineligible by investigators.