Efficacy and safety of zanubrutinib plus R-CHOP in treatment of non-GCB DLBCL with extranodal involvement
IntroductionTreatment 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...
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Frontiers Media S.A.
2023-08-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1219167/full |
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| author | Hongzhi Geng Hongzhi Geng Sixun Jia Ying Zhang Ying Zhang Jiaqi Li Jiaqi Li Jiaqi Li Jiaqi Li Qin Yang Qin Yang Liangyu Zeng Liangyu Zeng Xiangping Zong Xiangping Zong Xiangping Zong Xiangping Zong Yutong Lu Yutong Lu Yutong Lu Yutong Lu Shuangzhu Lu Shuangzhu Lu Shuangzhu Lu Shuangzhu Lu Jin Zhou Jin Zhou Jin Zhou Jin Zhou Caixia Li Caixia Li Caixia Li Caixia Li Depei Wu Depei Wu Depei Wu Depei Wu |
| author_facet | Hongzhi Geng Hongzhi Geng Sixun Jia Ying Zhang Ying Zhang Jiaqi Li Jiaqi Li Jiaqi Li Jiaqi Li Qin Yang Qin Yang Liangyu Zeng Liangyu Zeng Xiangping Zong Xiangping Zong Xiangping Zong Xiangping Zong Yutong Lu Yutong Lu Yutong Lu Yutong Lu Shuangzhu Lu Shuangzhu Lu Shuangzhu Lu Shuangzhu Lu Jin Zhou Jin Zhou Jin Zhou Jin Zhou Caixia Li Caixia Li Caixia Li Caixia Li Depei Wu Depei Wu Depei Wu Depei Wu |
| author_sort | Hongzhi Geng |
| collection | DOAJ |
| description | IntroductionTreatment 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.MethodsIn 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.ResultsFrom 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%).ConclusionZR-CHOP is safe and effective for treating treatment naïve non-GCB DLBCL patients with extranodal involvement.Clinical Trial RegistrationClinicaltrials.gov, NCT04835870 |
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| language | English |
| last_indexed | 2024-03-12T14:04:08Z |
| publishDate | 2023-08-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-d45b037915fd472cadcc83da2e8853b82023-08-21T15:53:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.12191671219167Efficacy and safety of zanubrutinib plus R-CHOP in treatment of non-GCB DLBCL with extranodal involvementHongzhi Geng0Hongzhi Geng1Sixun Jia2Ying Zhang3Ying Zhang4Jiaqi Li5Jiaqi Li6Jiaqi Li7Jiaqi Li8Qin Yang9Qin Yang10Liangyu Zeng11Liangyu Zeng12Xiangping Zong13Xiangping Zong14Xiangping Zong15Xiangping Zong16Yutong Lu17Yutong Lu18Yutong Lu19Yutong Lu20Shuangzhu Lu21Shuangzhu Lu22Shuangzhu Lu23Shuangzhu Lu24Jin Zhou25Jin Zhou26Jin Zhou27Jin Zhou28Caixia Li29Caixia Li30Caixia Li31Caixia Li32Depei Wu33Depei Wu34Depei Wu35Depei Wu36National Clinical Research Center for Hematologic Diseases, Suzhou, ChinaJiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Hematology, Affiliated Zhongshan Hospital of Dalian University, Dalian, ChinaNational Clinical Research Center for Hematologic Diseases, Suzhou, ChinaJiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Suzhou, ChinaJiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Suzhou University Medical College, Suzhou, ChinaCollaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Suzhou, ChinaJiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Suzhou, ChinaJiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Suzhou, ChinaJiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Suzhou University Medical College, Suzhou, ChinaCollaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Suzhou, ChinaJiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Suzhou University Medical College, Suzhou, ChinaCollaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Suzhou, ChinaJiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Suzhou University Medical College, Suzhou, ChinaCollaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Suzhou, ChinaJiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Suzhou University Medical College, Suzhou, ChinaCollaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Suzhou, ChinaJiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Suzhou University Medical College, Suzhou, ChinaCollaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Suzhou, ChinaJiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Suzhou University Medical College, Suzhou, ChinaCollaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaIntroductionTreatment 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.MethodsIn 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.ResultsFrom 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%).ConclusionZR-CHOP is safe and effective for treating treatment naïve non-GCB DLBCL patients with extranodal involvement.Clinical Trial RegistrationClinicaltrials.gov, NCT04835870https://www.frontiersin.org/articles/10.3389/fimmu.2023.1219167/fullzanubrutinibuntreated non-GCB DLBCLextranodal involvementanti-tumor activityoncogenic mutations |
| spellingShingle | Hongzhi Geng Hongzhi Geng Sixun Jia Ying Zhang Ying Zhang Jiaqi Li Jiaqi Li Jiaqi Li Jiaqi Li Qin Yang Qin Yang Liangyu Zeng Liangyu Zeng Xiangping Zong Xiangping Zong Xiangping Zong Xiangping Zong Yutong Lu Yutong Lu Yutong Lu Yutong Lu Shuangzhu Lu Shuangzhu Lu Shuangzhu Lu Shuangzhu Lu Jin Zhou Jin Zhou Jin Zhou Jin Zhou Caixia Li Caixia Li Caixia Li Caixia Li Depei Wu Depei Wu Depei Wu Depei Wu Efficacy and safety of zanubrutinib plus R-CHOP in treatment of non-GCB DLBCL with extranodal involvement Frontiers in Immunology zanubrutinib untreated non-GCB DLBCL extranodal involvement anti-tumor activity oncogenic mutations |
| title | Efficacy and safety of zanubrutinib plus R-CHOP in treatment of non-GCB DLBCL with extranodal involvement |
| title_full | Efficacy and safety of zanubrutinib plus R-CHOP in treatment of non-GCB DLBCL with extranodal involvement |
| title_fullStr | Efficacy and safety of zanubrutinib plus R-CHOP in treatment of non-GCB DLBCL with extranodal involvement |
| title_full_unstemmed | Efficacy and safety of zanubrutinib plus R-CHOP in treatment of non-GCB DLBCL with extranodal involvement |
| title_short | Efficacy and safety of zanubrutinib plus R-CHOP in treatment of non-GCB DLBCL with extranodal involvement |
| title_sort | efficacy and safety of zanubrutinib plus r chop in treatment of non gcb dlbcl with extranodal involvement |
| topic | zanubrutinib untreated non-GCB DLBCL extranodal involvement anti-tumor activity oncogenic mutations |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1219167/full |
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