294 | CLINICAL PRACTICE PATTERN AND OUTCOMES IN DLBCL WITH DISTINCT GENETIC SUBTYPES: A LARGE‐SCALE REAL‐WORLD STUDY FROM CHINA

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Introduction: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogenous disease, with genetic subtypes such as MCD, BN2, N1, EZB, A53 and ST2 (per LymphGen classification) (Wright et al., Cancer Cell2020).LymphPlex is a simplified 38-gene algorithm, identifies subtypes including TP53Mut, MCD-like, BN2-like, N1-like, EZB-like and ST2-like, showing high concordance with LymphGen (Shen et al., Sig Transduct Target Ther 2023).These subtypes exhibit distinct clinical characteristics and prognosis.GUIDANCE-01 trial showed promising results that genetic subtype-guided immunochemotherapy (R-CHOP-X) improves outcomes in DLBCL (Zhang et al.Cancer Cell 2023).Despite advances in molecular stratification and genetically guided treatment, real-world evidence on treatment patterns and outcomes about these subtypes remains unilluminated.This multi-center, nationwide study across China aimed to characterize clinical practice variability and therapeutic efficacy in a large DLBCL cohort stratified by genetic subtypes, offering insights to optimize precision therapy.Methods: Patients with genetically defined DLBCL subtypes were enrolled from 25 Chinese centers in this real-world study (NCT06026488).Data including clinical baseline characteristics, genetic profiles, therapeutic regimens, response assessments and survival outcomes of patients were collected retrospectively.The efficacy outcomes included progression-free survival (PFS), objective response rate (ORR), complete response rate (CRR) and overall survival (OS) et al.Results: By February 28, 2025, 3280 patients with DLBCL (median age: 60 years; 52.9% male) were analyzed.Most patients had advanced-stage disease (Ann Arbor III/IV disease, 55.7%), non-GCB disease (54.8%), extranodal involvement (46.3%), and ECOG performance status of 0-1 (83.6%).Common genetic subtypes included TP53 Mut , (18.5%), MCD-like (15.2%), and BN2-like (8.5%).High-risk features, such as MYC/BCL-2 dual expression and double-hit/triple-hit were observed in 28.1% and 3.9% of patients, respectively.Among them, the most commonly used first-line treatments comprised R-CHOP/R-CHOP-like (73.5%),R-CHOP plus targeted agents (6.5%) and R-DA-EPOCH (1.4%).2.9% of patients received CAR-T cell therapy, and 10.9% underwent autologous stem cell transplantation.Survival data collection is ongoing.Conclusions: This large-scale real-world study elucidates the clinical practice heterogeneity and outcomes across DLBCL with distinct genetic subtypes in a large cohort of Chinese patients, providing valuable insights for advancing precision therapy to improve clinical outcomes.

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