Bispecific Antibody-Based Salvage Therapy Followed by CAR-T ± ASCT in R/R Aggressive B-Cell Lymphoma

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.