GENETIC SUBTYPE GUIDED RITUXIMAB?BASED IMMUNOCHEMOTHERAPY IMPROVES OUTCOME IN NEWLY DIAGNOSED DIFFUSE LARGE B?CELL LYMPHOMA: FIRST REPORT OF A RANDOMIZED PHASE 2 STUDY

Introduction: Genetic subtypes of diffuse large B-cell lymphoma (DLBCL) have distinct oncogenic pathway feature, gene expression phenotype, and variable clinical outcome. We aimed to investigate whether adding novel targeted agents R-CHOP (R-CHOP-X) based on genetic could improve efficacy in newly diagnosed DLBCL. Methods: This was a randomized phase II study comparing R-CHOP-X with DLBCL (NCT04025593). Eligible patients were aged 18-80 years, IPI risk intermediate or high (IPI?2). All treated standard for the first cycle, 1:1 remaining 5 cycles. Targeted sequencing performed formalin-fixed paraffin-embedded tumor samples at diagnosis. used simplified method classify into six MCD, BN2, N1, EZB, TP53 NOS, using mutations 18 genes, BCL2 translocation, BCL6 fusion. MCD BN2 BTK inhibitor ibrutinib 420 mg/d, N1 NOS immunomodulatory agent lenalidomide 25mg d1-10, EZB histone deacetylase tucidinostat 20mg d1, 4, 8, 11, intravenous demethylating decitabine 10 mg/m2 d1-5 followed by R-CHOP. The primary endpoint complete response rate. Secondary endpoints included progression-free survival (PFS), overall (OS), rate, safety. Results: A total 128 enrolled (n = 64 per arm) between July 17th, 2019 December 29th, 2020. Baseline characteristics similar arms, median age (range 25-74), 52% male, 83% ECOG 0-1, 77% stage III/IV, 65% IPI?3 all patients. According Hans algorithm, 62% categorized as non-germinal subtype 36% MYC/BCL2 double expression. Regarding subtypes, 20%, 18%, 4%, 2%, 16% 39% classified TP53, subtype, respectively. Until March 1st, 2021, received least 3 cycles immunochemotherapy 107 available evaluation. rates 85% 91% arm, 72% With follow-up 14.1 months, 1-year PFS OS 96% 98% 79% 94% respectively (PFS: HR 0.22, 95%CI 0.09-0.61; OS: 0.28, 0.05-1.60). most common grade 3/4 adverse events (AEs) vs neutropenia (81% 75%), thrombocytopenia (31% 11%), anemia (25% 20%), febrile (20% 11%). For non-hematological AEs, infection occurred 3% gastrointestinal bleeding 2% No 4 AEs observed. Conclusion: guided showed encouraging outcome Keywords: Aggressive non-Hodgkin lymphoma, Molecular Therapies conflicts interests pertinent abstract.