PMID- 37671152 OWN - NLM STAT- MEDLINE DCOM- 20230907 LR - 20230915 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 14 DP - 2023 TI - Efficacy and safety of zanubrutinib plus R-CHOP in treatment of non-GCB DLBCL with extranodal involvement. PG - 1219167 LID - 10.3389/fimmu.2023.1219167 [doi] LID - 1219167 AB - INTRODUCTION: Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) shows poor response rates in non-germinal center B cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL) patients with multiple extranodal involvement. This study aims to evaluate anti-tumor activity and safety of zanubrutinib with R-CHOP (ZR-CHOP) in treatment naive non-GCB DLBCL with extranodal involvement. METHODS: In this single-arm, phase 2, prospective, single-center study, patients with newly diagnosed non-GCB DLBCL with extranodal involvement enrolled between October 2020 to March 2022 received ZR-CHOP for 6 cycles followed by 2 cycles of maintenance treatment with rituximab and zanubrutinib. The primary endpoint included progression-free survival (PFS) in the intent-to-treat (ITT) population whereas the secondary endpoints included overall response rate (ORR), complete response (CR), and duration of response. Further, next-generation sequencing (NGS) was used for detection of different oncogenic mutations closely related to DLBCL pathogenesis. RESULTS: From October 2020 to March 2022, 26 patients were enrolled, and 23 of them were evaluated for efficacy after receiving 3 cycles of ZR-CHOP treatment. 1-year PFS and OS were 80.8% and 88.5% respectively while expected PFS and OS for 2-years are 74.0% and 88.5% respectively with median follow-up of 16.7 months and ORR was 91.3% (CR: 82.61%; PR: 8.70%). Oncogenic mutations closely related to DLBCL pathogenesis were assessed in 20 patients using NGS. B-cell receptor and NF-kappaB pathway gene mutations were detected in 10 patients, which occurred in MYD88 (7/19), CD79B (4/19), CARD11 (5/19), and TNFAIP3 (2/19). Hematological adverse events (AEs) >/= grade 3 included neutropenia (50%), thrombocytopenia (23.1%), and anemia (7.7%) whereas non-hematological AEs >/= grade 3 included pulmonary infection (19.2%). CONCLUSION: ZR-CHOP is safe and effective for treating treatment naive non-GCB DLBCL patients with extranodal involvement. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT04835870. CI - Copyright (c) 2023 Geng, Jia, Zhang, Li, Yang, Zeng, Zong, Lu, Lu, Zhou, Li and Wu. FAU - Geng, Hongzhi AU - Geng H AD - National Clinical Research Center for Hematologic Diseases, Suzhou, China. AD - Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China. FAU - Jia, Sixun AU - Jia S AD - Department of Hematology, Affiliated Zhongshan Hospital of Dalian University, Dalian, China. FAU - Zhang, Ying AU - Zhang Y AD - National Clinical Research Center for Hematologic Diseases, Suzhou, China. AD - Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China. FAU - Li, Jiaqi AU - Li J AD - National Clinical Research Center for Hematologic Diseases, Suzhou, China. AD - Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Suzhou University Medical College, Suzhou, China. AD - Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. FAU - Yang, Qin AU - Yang Q AD - National Clinical Research Center for Hematologic Diseases, Suzhou, China. AD - Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China. FAU - Zeng, Liangyu AU - Zeng L AD - National Clinical Research Center for Hematologic Diseases, Suzhou, China. AD - Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China. FAU - Zong, Xiangping AU - Zong X AD - National Clinical Research Center for Hematologic Diseases, Suzhou, China. AD - Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Suzhou University Medical College, Suzhou, China. AD - Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. FAU - Lu, Yutong AU - Lu Y AD - National Clinical Research Center for Hematologic Diseases, Suzhou, China. AD - Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Suzhou University Medical College, Suzhou, China. AD - Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. FAU - Lu, Shuangzhu AU - Lu S AD - National Clinical Research Center for Hematologic Diseases, Suzhou, China. AD - Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Suzhou University Medical College, Suzhou, China. AD - Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. FAU - Zhou, Jin AU - Zhou J AD - National Clinical Research Center for Hematologic Diseases, Suzhou, China. AD - Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Suzhou University Medical College, Suzhou, China. AD - Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. FAU - Li, Caixia AU - Li C AD - National Clinical Research Center for Hematologic Diseases, Suzhou, China. AD - Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Suzhou University Medical College, Suzhou, China. AD - Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. FAU - Wu, Depei AU - Wu D AD - National Clinical Research Center for Hematologic Diseases, Suzhou, China. AD - Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China. AD - Institute of Blood and Marrow Transplantation, Suzhou University Medical College, Suzhou, China. AD - Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. LA - eng SI - ClinicalTrials.gov/NCT04835870 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230821 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - AG9MHG098Z (zanubrutinib) RN - 4F4X42SYQ6 (Rituximab) RN - 8N3DW7272P (Cyclophosphamide) SB - IM MH - Humans MH - Prospective Studies MH - Rituximab MH - *Lymphoma, Large B-Cell, Diffuse MH - B-Lymphocytes MH - Cyclophosphamide PMC - PMC10476090 OTO - NOTNLM OT - anti-tumor activity OT - extranodal involvement OT - oncogenic mutations OT - untreated non-GCB DLBCL OT - zanubrutinib COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/09/06 06:42 MHDA- 2023/09/07 06:42 PMCR- 2023/01/01 CRDT- 2023/09/06 03:53 PHST- 2023/05/08 00:00 [received] PHST- 2023/07/10 00:00 [accepted] PHST- 2023/09/07 06:42 [medline] PHST- 2023/09/06 06:42 [pubmed] PHST- 2023/09/06 03:53 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2023.1219167 [doi] PST - epublish SO - Front Immunol. 2023 Aug 21;14:1219167. doi: 10.3389/fimmu.2023.1219167. eCollection 2023.