Efficacy of individualized orelabrutinib-based regimens in relapsed or refractory central nervous system lymphoma

BackgroundRelapsed or refractory central nervous system lymphoma (rrCNSL) lacks established preferred treatment and carries an inferior prognosis. Bruton’s tyrosine kinase inhibitor (BTKi) showed promising effectiveness. Orelabrutinib is a second-generation BTKi with a high concentration in cerebros...

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Main Authors: Yuchen Wu, Xuefei Sun, Liwei Lv, Qu Cui, Jun Qian, Ruixian Xing, Xueyan Bai, Yuedan Chen, Qing Liu, Wenyuan Lai, Chunji Gao, Shengjun Sun, Nan Ji, Yuanbo Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Neurology
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Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2025.1570224/full
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author Yuchen Wu
Xuefei Sun
Liwei Lv
Qu Cui
Jun Qian
Ruixian Xing
Xueyan Bai
Yuedan Chen
Qing Liu
Wenyuan Lai
Chunji Gao
Shengjun Sun
Nan Ji
Yuanbo Liu
author_facet Yuchen Wu
Xuefei Sun
Liwei Lv
Qu Cui
Jun Qian
Ruixian Xing
Xueyan Bai
Yuedan Chen
Qing Liu
Wenyuan Lai
Chunji Gao
Shengjun Sun
Nan Ji
Yuanbo Liu
author_sort Yuchen Wu
collection DOAJ
description BackgroundRelapsed or refractory central nervous system lymphoma (rrCNSL) lacks established preferred treatment and carries an inferior prognosis. Bruton’s tyrosine kinase inhibitor (BTKi) showed promising effectiveness. Orelabrutinib is a second-generation BTKi with a high concentration in cerebrospinal fluid.MethodsIn this retrospective analysis, the outcomes of 37 relapsed or refractory central nervous system diffuse large B-cell lymphoma patients who received orelabrutinib, high-dose methotrexate, ifosfamide, etoposide, and dexamethasone (Ore-MIED) or orelabrutinib, high-dose methotrexate, temozolomide and dexamethasone (Ore-MTD) were evaluated.ResultsOf the 37 patients included, 11 received Ore-MTD, and 26 received the Ore-MIED regimen. The overall response rate in our cohort was 89.2%, with complete remission achieved in 51.4% of patients and partial remission in 37.8% of patients. The median progression-free survival was observed to be 7.0 months. No statistically significant difference was found in the median progression-free survival between patients receiving different treatment regimens (5.0 months for Ore-MTD versus 13.0 months for Ore-MIED; p = 0.29). Moreover, the median overall survival has not been reached in this cohort, indicating a promising outcome despite the aggressive nature of the disease.ConclusionOur study confirms the effectiveness and safety of Ore-MIED/Ore-MTD in rrCNSL patients, even in those with previous exposure to multiple lines of treatment.
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spelling doaj-art-477ae0e4fc0144a3b2c0c9abe5ec0d632025-08-20T03:07:44ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-06-011610.3389/fneur.2025.15702241570224Efficacy of individualized orelabrutinib-based regimens in relapsed or refractory central nervous system lymphomaYuchen Wu0Xuefei Sun1Liwei Lv2Qu Cui3Jun Qian4Ruixian Xing5Xueyan Bai6Yuedan Chen7Qing Liu8Wenyuan Lai9Chunji Gao10Shengjun Sun11Nan Ji12Yuanbo Liu13Department of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaDepartment of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Hematology, Chinese PLA General Hospital, Beijing, ChinaNeuroimaging Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBackgroundRelapsed or refractory central nervous system lymphoma (rrCNSL) lacks established preferred treatment and carries an inferior prognosis. Bruton’s tyrosine kinase inhibitor (BTKi) showed promising effectiveness. Orelabrutinib is a second-generation BTKi with a high concentration in cerebrospinal fluid.MethodsIn this retrospective analysis, the outcomes of 37 relapsed or refractory central nervous system diffuse large B-cell lymphoma patients who received orelabrutinib, high-dose methotrexate, ifosfamide, etoposide, and dexamethasone (Ore-MIED) or orelabrutinib, high-dose methotrexate, temozolomide and dexamethasone (Ore-MTD) were evaluated.ResultsOf the 37 patients included, 11 received Ore-MTD, and 26 received the Ore-MIED regimen. The overall response rate in our cohort was 89.2%, with complete remission achieved in 51.4% of patients and partial remission in 37.8% of patients. The median progression-free survival was observed to be 7.0 months. No statistically significant difference was found in the median progression-free survival between patients receiving different treatment regimens (5.0 months for Ore-MTD versus 13.0 months for Ore-MIED; p = 0.29). Moreover, the median overall survival has not been reached in this cohort, indicating a promising outcome despite the aggressive nature of the disease.ConclusionOur study confirms the effectiveness and safety of Ore-MIED/Ore-MTD in rrCNSL patients, even in those with previous exposure to multiple lines of treatment.https://www.frontiersin.org/articles/10.3389/fneur.2025.1570224/fullcentral nervous system lymphomarelapsed or refractoryBruton’s tyrosine kinase inhibitororelabrutinibmethotrexate
spellingShingle Yuchen Wu
Xuefei Sun
Liwei Lv
Qu Cui
Jun Qian
Ruixian Xing
Xueyan Bai
Yuedan Chen
Qing Liu
Wenyuan Lai
Chunji Gao
Shengjun Sun
Nan Ji
Yuanbo Liu
Efficacy of individualized orelabrutinib-based regimens in relapsed or refractory central nervous system lymphoma
Frontiers in Neurology
central nervous system lymphoma
relapsed or refractory
Bruton’s tyrosine kinase inhibitor
orelabrutinib
methotrexate
title Efficacy of individualized orelabrutinib-based regimens in relapsed or refractory central nervous system lymphoma
title_full Efficacy of individualized orelabrutinib-based regimens in relapsed or refractory central nervous system lymphoma
title_fullStr Efficacy of individualized orelabrutinib-based regimens in relapsed or refractory central nervous system lymphoma
title_full_unstemmed Efficacy of individualized orelabrutinib-based regimens in relapsed or refractory central nervous system lymphoma
title_short Efficacy of individualized orelabrutinib-based regimens in relapsed or refractory central nervous system lymphoma
title_sort efficacy of individualized orelabrutinib based regimens in relapsed or refractory central nervous system lymphoma
topic central nervous system lymphoma
relapsed or refractory
Bruton’s tyrosine kinase inhibitor
orelabrutinib
methotrexate
url https://www.frontiersin.org/articles/10.3389/fneur.2025.1570224/full
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