Pirtobrutinib+Pola-R-CHP for Newly Diagnosed Non-GCB DLBCL

Inclusion Criteria:

1. Histologically confirmed Non-GCB DLBCL (per 2016 WHO diagnostic criteria);
2. Whole-body PET/CT performed within 28 days prior to study enrollment demonstrating at least one measurable lesion (per 2014 Lugano criteria);
3. Age 18-65 years, with expected survival >3 months;
4. No prior anti-lymphoma treatment;
5. Signed written informed consent and ability to comply with protocol-required visits and procedures;
6. ECOG performance status 0-2;

7. Adequate organ and bone marrow function, defined as follows:

   • Hematology: Absolute neutrophil count (ANC) ≥1×10⁹/L, platelet count (PLT) ≥50×10⁹/L, hemoglobin (HGB) ≥8.0 g/dL; no granulocyte colony-stimulating factor, platelet transfusion, or red blood cell transfusion within 7 days prior to testing;
   • Hepatic function: Total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN;
   • Renal function: Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (CCR) ≥50 mL/min;
   • Cardiac function: NYHA Class III or below; left ventricular ejection fraction ≥50% by echocardiography;
   • Coagulation: International normalized ratio (INR) ≤1.5×ULN, activated partial thromboplastin time (APTT) ≤ULN +10s, and prothrombin time (PT) ≤ULN +3s;
8. Women of childbearing potential or male subjects with partners of childbearing potential must use effective contraception throughout the treatment period and for 90 days after the last dose.

Exclusion Criteria:

1. Central nervous system involvement;
2. History of hypersensitivity to the study drug, drugs of the same class, or excipients;
3. Concurrent malignancy requiring treatment or intervention;
4. Major surgery within 4 weeks prior to treatment (excluding vascular access catheter placement or biopsy);
5. Presence of any life-threatening disease, medical condition, or organ system dysfunction that, in the investigator's opinion, may affect patient safety or compliance with study procedures;
6. Uncontrolled cardiac symptoms or disease, including: i. NYHA Class II or higher heart failure; ii. Unstable angina; iii. Myocardial infarction within 1 year; iv. Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention;
7. Active bleeding;
8. Active, uncontrolled systemic bacterial, viral, fungal, or parasitic infection (excluding onychomycosis), or other clinically significant active disease process that, in the investigator's opinion, renders the patient unsuitable for clinical trial participation;
9. Known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome;
10. Exclusion of patients with active chronic hepatitis B or active hepatitis C. Patients with positive hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C virus antibody at screening must undergo further HBV-DNA and HCV-RNA testing. Patients with stable hepatitis B (HBV-DNA <2500 copies/mL or 500 IU/mL) on antiviral therapy and cured hepatitis C patients (below the limit of detection) may be enrolled;
11. Definitive history of neurological or psychiatric disorder, including epilepsy or dementia;
12. Pregnant or lactating women;
13. Receipt of other investigational agents within 1 month prior to first dose;
14. Any other factors that, in the investigator's opinion, may affect the evaluation of efficacy or safety in this study.