Improved efficacy of Orelabrutinib plus Rituximab, Temozolomide and High-Dose Methotrexate (RMOT) vs. RMT in untreated primary CNS lymphoma: A matched analysis

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ID: 332257
2026
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Abstract
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 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 = 0.026) and had superior PFS (HR 0.357, 95% CI 0.150-0.850, P = 0.015). These benefits remained after PSM. RMOT regimen was associated with significantly longer PFS of patients with non-GCB subtype (HR 0.274, 95% CI 0.081-0.932, P=0.027). 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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Authors Peng Zhang, Man Nie, Hang Yang, Xiaojie Fang, Chengxi He, Dongyu Zhuang, Honglian Liu, Silan Huang, Dexin Lei, Qingqing Cai, Yi Xia
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Journal Neuro-Oncology Advances
Year 2026
DOI
10.1093/noajnl/vdag262
URL
https://doi.org/10.1093/noajnl/vdag262
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