Brentuximab Vedotin Combined With R-CHP in Newly Diagnosed EBV+ DLBCL-NOS

Inclusion Criteria:

\- Patients must meet all of the following inclusion criteria to be eligible for enrollment:

1. BV+DLBCL, NOS diagnosed by pathological diagnosis according to WHO 2016 classification criteria;
2. Sign the informed consent form;
3. Systemic PET/CT performed within 28 days prior to enrollment demonstrating at least one measurable lesion in two perpendicular dimensions (nodal lesion: longest diameter \>15 mm, short axis \>5 mm; extranodal lesion: longest diameter \>10 mm) per Lugano 2014 criteria;
4. ECOG Performance Status (PS) of 0-2;
5. Adequate organ and bone marrow function defined as:

   * Hematology: Absolute neutrophil count (ANC) ≥1.0×10⁹/L, platelet count (PLT) ≥50×10⁹/L, hemoglobin (HGB) ≥8.0 g/dL; without granulocyte colony-stimulating factor, platelet transfusion, or red blood cell transfusion within 7 days prior to testing.
   * Liver function: Total bilirubin (TBIL) ≤1.5×ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN.
   * Renal function: Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance rate (CCR) ≥50 mL/min.
   * Cardiac function: NYHA class \<III; left ventricular ejection fraction (LVEF) ≥50% by echocardiography.
   * Coagulation: International normalized ratio (INR) ≤1.5×ULN, activated partial thromboplastin time (APTT) ≤ULN +10 s, prothrombin time (PT) ≤ULN +3 s.
   * Thyroid function: Baseline thyroid-stimulating hormone (TSH) within normal range or abnormal TSH with normal T3/T4 levels and no clinical symptoms.
6. Expected survival ≥ 3 months.
7. Age 18-70 years.
8. For subjects of childbearing potential or with partners of childbearing potential: Agreement to use highly effective contraception during treatment and for 90 days after the last dose.

Exclusion Criteria:

* Patients who meet any of the following criteria will be excluded from the study：

  1. Central nervous system (CNS) involvement.
  2. Second primary malignancy (except cured non-melanoma skin cancer, superficial bladder cancer, cervical carcinoma in situ, gastrointestinal intramucosal carcinoma, or breast cancer with no recurrence within 5 years).
  3. History of severe allergic diseases, hypersensitivity to macromolecular protein preparations, or any component of Brentuximab Vedotin.
  4. Prior allogeneic organ transplant or hematopoietic stem cell transplantation.
  5. Concurrent systemic anti-tumor therapy during the study.
  6. Anti-cancer vaccines or immunostimulatory anti-tumor therapy within 3 months prior to enrollment.
  7. Active severe acute/chronic infection requiring systemic therapy.
  8. Active or history of autoimmune disease within 2 years (exceptions: vitiligo, psoriasis, alopecia, Graves' disease without systemic treatment in the past 2 years; hypothyroidism requiring thyroid hormone replacement only; type I diabetes controlled with insulin).
  9. Systemic immunosuppressive therapy within 4 weeks prior to enrollment (excluding topical/nasal/inhaled corticosteroids or physiologic doses ≤10 mg/day prednisone equivalent).
  10. Positive serology for HIV antibody (HIV-Ab), Treponema pallidum antibody (TP-Ab), HCV antibody (HCV-Ab); HBsAg-positive with HBV DNA \>ULN.
  11. History of idiopathic pulmonary fibrosis or interstitial pneumonia.
  12. Active tuberculosis.
  13. Prior ≥Grade 3 immune-related adverse events from immunotherapy.
  14. History of neurologic/psychiatric disorders (e.g., epilepsy, dementia).
  15. Administration of live vaccines (e.g., influenza, varicella) within 4 weeks prior to treatment or planned during the study.
  16. History of alcohol/drug abuse.
  17. Pregnancy or lactation.
  18. Participation in another interventional clinical trial within 1 month prior to enrollment.
  19. Other factors deemed by investigators to potentially compromise efficacy/safety assessments.