ORIGINAL RESEARCH article
Front. Oncol.
Sec. Hematologic Malignancies
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1669385
Ibrutinib Combined with Rituximab and High-Dose Methotrexate (IRM) in Newly Diagnosed Primary CNS Diffuse Large B-Cell Lymphoma: A Pilot Study with Long-Term Follow-Up
Provisionally accepted
Yixian Guo1
Yongzhi Shan1,2
Yueshan Piao1Xiaoli Chang1Dongmei Zou1Qiang Ma1Yukui Wei1,2Geng Xu1,2
Yaming Wang1,2Dandan Wang1Lianghong Teng1Chunxue Wu1Zhilian Zhao1Tianbin Song1Hong Zhao1Wuhan Hui1Li Su1Wanling Sun1*- 1Capital Medical University, Beijing, China
- 2China International Neuroscience Institute (China-INI), Beijing, China
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Background: Primary diffuse large B-cell lymphoma of the central nervous system (PCNS DLBCL) is a rare, aggressive lymphoma with rising incidence in elderly patients. Bruton tyrosine kinase (BTK) inhibitors show promise in recurrent/refractory cases, warranting exploration in newly diagnosed disease. Methods: This single-center pilot study evaluated the safety/efficacy of ibrutinib, rituximab, and high-dose methotrexate (IRM) in nine newly diagnosed PCNS DLBCL patients (2018 – 2019). Treatment included 4 cycles of IRM induction, consolidation (HSCT or 2 additional IRM cycles), and maintenance therapy (ibrutinib/lenalidomide). Results: After induction, overall response rate (ORR) was 100% (complete response [CR]: 77.8%, partial response [PR]: 22.2%). Post-consolidation, CR increased to 88.9%. At a median follow-up of 77.6 months, 5-year overall survival (OS) and progression-free survival (PFS) rates were both 77.8%, with 8 patients in sustained CR and one progression. No treatment-related deaths occurred; grade ≥3 adverse events were rare (2 neutropenia, 2 anemia, 1 gastrointestinal bleeding). Conclusion: In this small pilot cohort, IRM showed promising activity and tolerability as first-line therapy for PCNS DLBCL. These descriptive findings warrant confirmation in larger prospective trials (#ChiCTR1900027811).
Keywords: newly diagnosed, Primary diffuse large B-cell lymphoma of the CNS, Bruton tyrosine kinase inhibitor, Methotrexate, Ibrutinib
Received: 19 Jul 2025; Accepted: 12 Sep 2025.
Copyright: © 2025 Guo, Shan, Piao, Chang, Zou, Ma, Wei, Xu, Wang, Wang, Teng, Wu, Zhao, Song, Zhao, Hui, Su and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wanling Sun, Capital Medical University, Beijing, China
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