AUTHOR=Wu Yuchen , Sun Xuefei , Lv Liwei , Cui Qu , Qian Jun , Xing Ruixian , Bai Xueyan , Chen Yuedan , Liu Qing , Lai Wenyuan , Gao Chunji , Sun Shengjun , Ji Nan , Liu Yuanbo 

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

JOURNAL=Frontiers in Neurology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1570224

DOI=10.3389/fneur.2025.1570224

ISSN=1664-2295

ABSTRACT=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.