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.