ORIENT STUDY: REGIMEN OF ORELABRUTINIB PLUS R‐CHOP‐LIKE FOR PATIENTS WITH NEWLY DIAGNOSED UNTREATED NON‐GCB DLBCL

Introduction: Orelabrutinib (O), as a novel highly selective bruton tyrosine kinase inhibitors (BTKi), preserved NK-cell-mediated antibody-dependent cellular cytotoxicity (ADCC) induced by rituximab (R) and thus boost antitumor effect of R-based regimen. We aimed to analyze efficacy safety O plus R-CHOP-like (O+R-CHOP) for untreated non-germinal center B-cell-like diffuse large B-cell lymphoma (non-GCB DLBCL) patients (pts) who benefited from induction therapy R (OR). Methods: Pts with non-GCB DLBCL were enrolled in the ongoing, multicenter, phase II study (NCT05498259). received (150 mg/day) (375 mg/m2, day 1) at stage 21 days. Then, pts reduction lesion ≥25% + R-CHOP on 21-day cycle 6 cycles. Primary endpoint was complete remission (CR) rate after cycles O+R-CHOP. Secondary endpoints mini or better response (mRR, defined percentage CR, partial [PR], [miniR, 25%–50%]) OR, overall (ORR) progression-free survival O+R-CHOP, safety. Results: Eleven (median age, 62 years) cutoff date (March 6, 2023). Most had extranodal involvement (72.7%) MYC/BCL2 double expression (DEL, 54.5%). All III-IV disease. Among them, 5, 2, 1 pt detected MYD88, CD79A, TP53 mutations, respectively. 11 completed therapy, 10 attained response, mRR 90.9% (CR 36.4%; PR 45.5%; miniR 9.1%) then continued receive O+R-CHOP (median, 4 cycles). Seven (70.0%) ≥3 all achieved CR end 3; among whom (10.0%) sustained (Figure 1). Throughout 8 (80.0%) ORR 90.0%. No progressive disease death reported. By subgroup analysis stage, DEL (100.0% vs. 75.0%) than non-DEL. A similar result observed over those without (mRR 100.0% 66.7%). Besides, CRR 75.0%, respectively while MYD88 CD79A mutations obtained 80.0% 100.0%, At OR (36.4%) adverse events (AEs), grade 1–2 hematological AEs. AEs occurred pts, 3 (27.3%) (1 lymphocyte count decreased, pulmonary infection, white blood cell neutrophil decreased). deaths treatment discontinuation due observed. Encore Abstract - previously submitted EHA 2023 The research funded by: grants Health development-cancer prevention (BJHA-CPP-002), Top-notch young health talents, 5th Suzhou professionals program (GSWS2019035), National Clinical Research Center hematologic (2021ZKMC01). Keywords: Molecular Targeted Therapies, Lymphoid Cancers Other conflicts interests pertinent abstract.