Yang Yong, Yu Jing, Hu Xiao-Mei, Chen Si-Lin, Zhao Rui-Zhi, Huang Cheng, Guo Jiang-Rui, Tang Tian-Lan, Chen Cheng, Lin Yu-Ping, Wang Ying, Liu Tian-Xiu, Zheng Hao, Liao Si-Qin, Chen Jin-Hua, Fu Hai-Ying, Liu Ting-Bo
Department of Radiation Oncology Fujian Medical University Union Hospital, Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors (Fujian Medical University), Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological and Breast Malignancies) Fuzhou China.
Department of Pulmonary Oncology Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University Wuhan China.
MedComm (2020). 2025 May 25;6(6):e70225. doi: 10.1002/mco2.70225. eCollection 2025 Jun.
This open-label, single-arm phase II study assessed the safety and efficacy of sequential hypofractionated radiotherapy (RT) followed by zimberelimab and R-GemOx (rituximab, gemcitabine, oxaliplatin) in patients with primary refractory diffuse large B-cell lymphoma (DLBCL). Fourteen patients were enrolled between June 2022 and December 2023, with 13 included in the analysis. RT doses of 36 and 24 Gy were delivered to the gross and target volumes in 12 fractions, followed by zimberelimab and R-GemOx. The overall response rate within the irradiated field was 92.3%, and a complete response (CR) was achieved by 61.5% of patients; however, 38.5% experienced disease progression. Treatment-related toxicities were manageable, primarily comprising mild leukocytopenia. Digital spatial profiling revealed 53 differentially expressed genes in CD20-rich lymphoma regions and 93 in CD3-rich T cell regions in non-CR patients. Reactome analysis identified key immune system pathways. T cell infiltration correlated with treatment efficacy, and multiplex immunohistochemistry validated immune pathways as potential therapeutic targets. This study demonstrated the promising role of RT combined with immunochemotherapy in refractory DLBCL and suggests immune pathways as critical targets to improve treatment outcomes.
这项开放标签、单臂II期研究评估了序贯低分割放疗（RT）联合zimberelimab和R-GemOx（利妥昔单抗、吉西他滨、奥沙利铂）治疗原发性难治性弥漫性大B细胞淋巴瘤（DLBCL）患者的安全性和疗效。2022年6月至2023年12月期间共纳入14例患者，其中13例纳入分析。分别以12次分割向大体肿瘤体积和靶体积给予36 Gy和24 Gy的放疗剂量，随后给予zimberelimab和R-GemOx。照射野内的总缓解率为92.3%，61.5%的患者实现了完全缓解（CR）；然而，38.5%的患者出现疾病进展。治疗相关毒性易于管理，主要为轻度白细胞减少。数字空间分析显示，非CR患者中，富含CD20的淋巴瘤区域有53个差异表达基因，富含CD3的T细胞区域有93个差异表达基因。Reactome分析确定了关键的免疫系统通路。T细胞浸润与治疗疗效相关，多重免疫组化验证了免疫通路作为潜在治疗靶点。本研究证明了放疗联合免疫化疗在难治性DLBCL中的前景，并提示免疫通路是改善治疗结果的关键靶点。
