利妥昔单抗、环磷酰胺、阿霉素、长春新碱和泼尼松（R-CHOP）治疗对多个异型淋巴结外累及的非生发中心B细胞型（non-GCB）弥漫大B细胞淋巴瘤（DLBCL）患者的反应率低。本研究旨在评估Zanubrutinib联合R-CHOP（ZR-CHOP）治疗初治非生发中心GCB DLBCL的抗肿瘤活性和安全性以及额外淋巴结累及情况。 在这项单臂、2期、前瞻性、单中心研究中，于2020年10月至2022年3月期间入组的新诊断非生发中心GCB DLBCL患者接受了6个周期ZR-CHOP治疗，随后进行了2个周期的利妥昔单抗和Zanubrutinib维持治疗。主要终点为意向分析（ITT）人群的无进展生存期（PFS），而次要终点包括总体反应率（ORR）、完全缓解（CR）和持续反应时间。此外，通过下一代测序（NGS）检测与DLBCL发病机制密切相关的不同致癌突变。从2020年10月至2022年3月，共有26名患者入组，其中23名患者接受了3个周期的ZR-CHOP治疗后进行了疗效评估。1年的PFS率和总生存率分别为80.8%和88.5%，而预计的2年PFS率和总生存率分别为74.0%和88.5%。中位随访时间为16.7个月，ORR为91.3%（CR：82.61%，PR：8.70%）。通过NGS检测，对20名患者进行了与DLBCL发病机制密切相关的致癌突变评估。在19名患者中检测到与B细胞受体和NF-κB通路基因突变相关的突变，其中MYD88（7/19）、CD79B（4/19）、CARD11（5/19）和TNFAIP3（2/19）。 ≥3级的血液学不良事件（AEs）包括中性粒细胞减少（50%），血小板减少症（23.1%）和贫血（7.7%），而≥3级的非血液学不良事件包括肺部感染（19.2%）。ZR-CHOP对于初治非生发中心GCB DLBCL患者的额外淋巴结累及安全有效。Clinicaltrials.gov，NCT04835870。© 2023 Geng, Jia, Zhang, Li, Yang, Zeng, Zong, Lu, Lu, Zhou, Li and Wu.

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 naïve non-GCB DLBCL with extranodal involvement.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.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-κB 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%).ZR-CHOP is safe and effective for treating treatment naïve non-GCB DLBCL patients with extranodal involvement.Clinicaltrials.gov, NCT04835870.Copyright © 2023 Geng, Jia, Zhang, Li, Yang, Zeng, Zong, Lu, Lu, Zhou, Li and Wu.