This is a prospective, open-label, multicenter, randomized controlled study in participants with previously untreated large B-cell lymphoma. Participants will be stratified into different risk groups using an AI-based multimodal model. Those classified as intermediate- or high-risk will be randomized in a 1:1 ratio to receive either an AI-guided treatment strategy or Pola-R-CHP. In the experimental arm, participants will receive either genotype-guided targeted agents in combination with Pola-R-CHP or Pola-R-CHP combined with glofitamab, according to their AI-defined risk group and molecular features. Participants in the control arm will receive Pola-R-CHP. The study will evaluate the efficacy and safety of the AI-guided treatment strategy compared with Pola-R-CHP.

Inclusion Criteria:

• Age 18-75 years with comprehensive geriatric assessment stratified as fit
• Previously untreated participants with CD20-positive LBCL (without central nervous system involvement)
• ECOG Performance Status of 0, 1, or 2
• After 1 cycle of Pola-R-CHP, classified as intermediate-risk or high-risk by AI-based multimodal stratification
• Life expectancy ≥ 3 months
• At least 1 measurable site of disease (defined as lymph nodes with the long diameters longer than 1.5cm, or extra-nodal sites with the long diameters longer than 1.0cm; meanwhile, any lesion site with at least 2 measurable vertical diameters)
• The patient or his or her legal representative must provide written informed consent prior to any special examination or procedure for the research.
• Anti-lymphoma drugs have not been used before (except glucocorticoids)

Exclusion Criteria:

• Prior solid organ transplantation or SCT

• Significant or extensive history of cardiovascular disease such as New York Heart Association Class III or IV cardiac disease or Objective Assessment Class C or D, myocardial infarction within the last 6 months prior to the start of Cycle 1, unstable arrhythmias, or unstable angina

• History or presence of an abnormal ECG that is clinically significant in the investigator's opinion

• Any of the following abnormal laboratory values (unless any of these abnormalities are due to underlying lymphoma):

  • Absolute neutrophil count <1.0 × 10⁹/L.
  • Platelet count <75 × 10⁹/L
  • Serum AST and ALT ≥ 2.5 x ULN
  • Total bilirubin ≥ 1.5 x ULN
  • Serum creatinine clearance < 30 mL/min (using Cockcroft-Gault formula)

• Any active infection within 7 days prior to Cycle 1 Day 1 that would impact participant safety

• Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen [HBsAg] serology)：Participants with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HbsAg) may be included if hepatitis B virus (HBV) DNA is undetectable at the time of screening. Such participants must be willing to undergo HBV DNA testing every month and appropriate antiviral therapy as indicated

• Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing)：Participants positive for HCV antibody are eligible only if PCR is negative for HCV RNA

• Participants with a history of progressive multifocal leukoencephalopathy

• Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 12 months after final dose of treatment

• Participants with uncontrolled coagulation disorders, connective tissue diseases, severe infectious diseases

• Other concurrent and uncontrolled medical conditions that, in the opinion of the investigator, would affect the patient's participation in the study