Phase II Trial of Hypofractionated Radiotherapy and Immunochemotherapy in Primary Refractory Diffuse Large B‐Cell Lymphoma: Preliminary Results and Insights from Digital Spatial Profiling
ABSTRACT 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 patient...
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2025-06-01
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| Online Access: | https://doi.org/10.1002/mco2.70225 |
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| author | Yong Yang Jing Yu Xiao‐Mei Hu Si‐Lin Chen Rui‐Zhi Zhao Cheng Huang Jiang‐Rui Guo Tian‐Lan Tang Cheng Chen Yu‐Ping Lin Ying Wang Tian‐Xiu Liu Hao Zheng Si‐Qin Liao Jin‐Hua Chen Hai‐Ying Fu Ting‐Bo Liu |
| author_facet | Yong Yang Jing Yu Xiao‐Mei Hu Si‐Lin Chen Rui‐Zhi Zhao Cheng Huang Jiang‐Rui Guo Tian‐Lan Tang Cheng Chen Yu‐Ping Lin Ying Wang Tian‐Xiu Liu Hao Zheng Si‐Qin Liao Jin‐Hua Chen Hai‐Ying Fu Ting‐Bo Liu |
| author_sort | Yong Yang |
| collection | DOAJ |
| description | ABSTRACT 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. |
| format | Article |
| id | doaj-art-d6b79e3b2beb493f9f52e929f030b794 |
| institution | DOAJ |
| issn | 2688-2663 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-d6b79e3b2beb493f9f52e929f030b7942025-08-20T02:56:34ZengWileyMedComm2688-26632025-06-0166n/an/a10.1002/mco2.70225Phase II Trial of Hypofractionated Radiotherapy and Immunochemotherapy in Primary Refractory Diffuse Large B‐Cell Lymphoma: Preliminary Results and Insights from Digital Spatial ProfilingYong Yang0Jing Yu1Xiao‐Mei Hu2Si‐Lin Chen3Rui‐Zhi Zhao4Cheng Huang5Jiang‐Rui Guo6Tian‐Lan Tang7Cheng Chen8Yu‐Ping Lin9Ying Wang10Tian‐Xiu Liu11Hao Zheng12Si‐Qin Liao13Jin‐Hua Chen14Hai‐Ying Fu15Ting‐Bo Liu16Department 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 ChinaDepartment of Pulmonary Oncology Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University Wuhan ChinaDepartment of Pathology Fujian Medical University Union Hospital Fuzhou ChinaDepartment 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 ChinaDepartment 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 ChinaDepartment 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 ChinaDepartment of Hematology Fujian Medical University Union Hospital, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology Fuzhou ChinaDepartment 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 ChinaDepartment 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 ChinaDepartment 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 ChinaDepartment 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 ChinaDepartment 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 ChinaDepartment 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 ChinaDepartment of PET/CT Fujian Medical University Union Hospital Fuzhou ChinaFollow‐Up Center Fujian Medical University Union Hospital Fuzhou ChinaDepartment of Hematology The Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, The Third People's Hospital of Fujian Province Fuzhou ChinaDepartment of Hematology Fujian Medical University Union Hospital, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology Fuzhou ChinaABSTRACT 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.https://doi.org/10.1002/mco2.70225diffuse large B‐cell lymphomaimmune systemprimary refractoryradiotherapyzimberelimab |
| spellingShingle | Yong Yang Jing Yu Xiao‐Mei Hu Si‐Lin Chen Rui‐Zhi Zhao Cheng Huang Jiang‐Rui Guo Tian‐Lan Tang Cheng Chen Yu‐Ping Lin Ying Wang Tian‐Xiu Liu Hao Zheng Si‐Qin Liao Jin‐Hua Chen Hai‐Ying Fu Ting‐Bo Liu Phase II Trial of Hypofractionated Radiotherapy and Immunochemotherapy in Primary Refractory Diffuse Large B‐Cell Lymphoma: Preliminary Results and Insights from Digital Spatial Profiling MedComm diffuse large B‐cell lymphoma immune system primary refractory radiotherapy zimberelimab |
| title | Phase II Trial of Hypofractionated Radiotherapy and Immunochemotherapy in Primary Refractory Diffuse Large B‐Cell Lymphoma: Preliminary Results and Insights from Digital Spatial Profiling |
| title_full | Phase II Trial of Hypofractionated Radiotherapy and Immunochemotherapy in Primary Refractory Diffuse Large B‐Cell Lymphoma: Preliminary Results and Insights from Digital Spatial Profiling |
| title_fullStr | Phase II Trial of Hypofractionated Radiotherapy and Immunochemotherapy in Primary Refractory Diffuse Large B‐Cell Lymphoma: Preliminary Results and Insights from Digital Spatial Profiling |
| title_full_unstemmed | Phase II Trial of Hypofractionated Radiotherapy and Immunochemotherapy in Primary Refractory Diffuse Large B‐Cell Lymphoma: Preliminary Results and Insights from Digital Spatial Profiling |
| title_short | Phase II Trial of Hypofractionated Radiotherapy and Immunochemotherapy in Primary Refractory Diffuse Large B‐Cell Lymphoma: Preliminary Results and Insights from Digital Spatial Profiling |
| title_sort | phase ii trial of hypofractionated radiotherapy and immunochemotherapy in primary refractory diffuse large b cell lymphoma preliminary results and insights from digital spatial profiling |
| topic | diffuse large B‐cell lymphoma immune system primary refractory radiotherapy zimberelimab |
| url | https://doi.org/10.1002/mco2.70225 |
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