Improved efficacy of orelabrutinib plus rituximab, temozolomide and high-dose methotrexate versus rituximab, high-dose methotrexate plus temozolomide in untreated primary CNS lymphoma: A matched analysis
Abstract
Background: Primary central nervous system lymphoma (PCNSL) is a rare, aggressive malignant tumor with poor prognosis, and the optimal standard treatment remains undefined. This study aimed to compare the efficacy and safety of rituximab, high-dose methotrexate plus temozolomide (RMT regimen) and orelabrutinib plus RMT (RMOT regimen) in patients with newly diagnosed PCNSL.
Methods: This retrospective study enrolled adult patients with histologically confirmed PCNSL who had received induction treatment with the RMT regimen or the novel combination regimen of orelabrutinib. Progression-free survival (PFS) and overall survival (OS) were analyzed using Cox proportional hazards models. Propensity score matching (PSM) was performed to balance baseline characteristics between the treatment groups.
Results: A total of 101 patients were included in the analysis. The median age was 59 years, and most were of the non-germinal center B-cell (non-GCB) subtype (62.4%) and deep structural involvement (64.4%). The RMOT group was associated with a higher complete response rate than the RMT group (84.8% vs 63.2%, P = .026) and had superior PFS (HR 0.357, 95% CI 0.150-0.850, P = .015). These benefits remained after PSM. RMOT regimen was associated with significantly longer PFS in patients with the non-GCB subtype (HR 0.274, 95% CI 0.081-0.932, P = .027). Adverse events were primarily grade 1-2, and no treatment-related deaths occurred in either group.
Conclusions: This retrospective study suggested that RMOT was associated with higher CRR and longer PFS compared to RMT, particularly in non-GCB subtype patients, with a tolerable safety profile, and has the potential to become a new optional regimen for clinical practice.
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BibTeX
@article{zhang2026improved,
title = {{Improved efficacy of orelabrutinib plus rituximab, temozolomide and high-dose methotrexate versus rituximab, high-dose methotrexate plus temozolomide in untreated primary CNS lymphoma: A matched analysis}},
author = {Peng Zhang and Man Nie and Hang Yang and Xiaojie Fang and Chengxi He and Dongyu Zhuang and Honglian Liu and Silan Huang and Dexin Lei and Qingqing Cai and Yi Xia},
journal = {Neuro-Oncology Advances},
year = {2026},
month = oct,
doi = {10.1093/noajnl/vdag262},
url = {https://doi.org/10.1093/noajnl/vdag262},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Improved efficacy of orelabrutinib plus rituximab, temozolomide and high-dose methotrexate versus rituximab, high-dose methotrexate plus temozolomide in untreated primary CNS lymphoma: A matched analysis
AU - Peng Zhang
AU - Man Nie
AU - Hang Yang
AU - Xiaojie Fang
AU - Chengxi He
AU - Dongyu Zhuang
AU - Honglian Liu
AU - Silan Huang
AU - Dexin Lei
AU - Qingqing Cai
AU - Yi Xia
PY - 2026
DA - 2026/10/12
JO - Neuro-Oncology Advances
DO - 10.1093/noajnl/vdag262
UR - https://doi.org/10.1093/noajnl/vdag262
AB - Background: Primary central nervous system lymphoma (PCNSL) is a rare, aggressive malignant tumor with poor prognosis, and the optimal standard treatment remains undefined. This study aimed to compare the efficacy and safety of rituximab, high-dose methotrexate plus temozolomide (RMT regimen) and orelabrutinib plus RMT (RMOT regimen) in patients with newly diagnosed PCNSL. Methods: This retrospective study enrolled adult patients with histologically confirmed PCNSL who had received induction treatment with the RMT regimen or the novel combination regimen of orelabrutinib. Progression-free survival (PFS) and overall survival (OS) were analyzed using Cox proportional hazards models. Propensity score matching (PSM) was performed to balance baseline characteristics between the treatment groups. Results: A total of 101 patients were included in the analysis. The median age was 59 years, and most were of the non-germinal center B-cell (non-GCB) subtype (62.4%) and deep structural involvement (64.4%). The RMOT group was associated with a higher complete response rate than the RMT group (84.8% vs 63.2%, P = .026) and had superior PFS (HR 0.357, 95% CI 0.150-0.850, P = .015). These benefits remained after PSM. RMOT regimen was associated with significantly longer PFS in patients with the non-GCB subtype (HR 0.274, 95% CI 0.081-0.932, P = .027). Adverse events were primarily grade 1-2, and no treatment-related deaths occurred in either group. Conclusions: This retrospective study suggested that RMOT was associated with higher CRR and longer PFS compared to RMT, particularly in non-GCB subtype patients, with a tolerable safety profile, and has the potential to become a new optional regimen for clinical practice.
SN - 2632-2498
ER -