AI-Driven Treatment Strategy vs ZR2 in Older Treatment-naive Patients With LBCL

This is a prospective, open-label, multicenter, randomized controlled study in older treatment-naive patients with LBCL. 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 ZR2. In the experimental arm, participants will receive polatuzumab vedotin in combination with ZR2 or Pola-ZR-Glo regimen (polatuzumab vedotin, zanubrutinib, lenalidomide, and glofitamab), according to their AI-defined risk group. Participants in the control arm will receive ZR2. The study will evaluate the efficacy and safety of the AI-guided treatment strategy compared with ZR2.

Inclusion Criteria: Patients must satisfy all of the following criteria to be enrolled in the study: * Histologically-confirmed large B-cell lymphoma (without central nervous system involvement) * Aged ≥ 70 years old with comprehensive geriatric assessment stratified as unfit or frail, or those who decline immunochemotherapy. * After 1 cycle of ZR2, classified as intermediate-risk or high-risk by AI-based multimodal stratification * Eastern Cooperative Oncology Group Performance Status 0-2 * 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) * Life expectancy of at least 3 months determined by researchers * 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: Presence of any of the following criteria will exclude a patient from enrollment: * Uncontrolled blood clotting disorders, connective tissue diseases, serious infectious diseases and other diseases * Laboratory measures meet the following criteria at screening (unless caused by lymphoma): Neutrophils\