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High-dose MTX-based polychemotherapy for primary CNS lymphoma in younger patients: Long-term efficacy of the modified Bonn protocol.

Neuro-oncology advances

Authors: Thomas Zeyen, Johannes Weller, Matthias Schneider, Anna-Laura Potthoff, Christina Schaub, Lea Roever, Eleni Gkika, Hartmut Vatter, Tobias A W Holderried, Peter Brossart, Ulrich Herrlinger, Niklas Schaefer

BACKGROUND: Polychemotherapy based on high-dose methotrexate (HD-MTX) is the standard therapy for newly diagnosed younger patients (<65 years) with primary CNS lymphoma (PCNSL). In the modified Bonn protocol, consolidation therapy consists of intraventricular chemotherapy that is added to the continuation of HD-MTX-based chemotherapy. This study investigates the efficacy and toxicity of the modified Bonn protocol in first-line therapy of young patients with PCNSL.

METHODS: All consecutive immunocompetent patients aged <65 years who were newly diagnosed with PCNSL from 2012 to 2021 and started first-line therapy with the modified Bonn protocol at the Neurooncology Center Bonn were included in this retrospective analysis. Treatment comprised 3 courses of rituximab/HD-MTX/IFO followed by consolidation therapy with 2 courses of HD-AraC and 2 courses of HD-MTX/IFO, including intrathecal MTX and intrathecal AraC. Progression-free and overall survival were evaluated.

RESULTS: Forty-three patients were included. Thirty-seven patients (86%) reached intrathecal consolidation therapy. Grade 3/4 toxicity was observed in 58.1%. The median PFS was 102.8 months; 5-year OS rate was 76% (median not reached). Eighteen patients developing refractory/relapsed PCNSL received second-line therapy using the modified Freiburg protocol (AraC/TT +/- HD-MTX/rituximab followed by BCNU/TT-based HD-ASCT). A second relapse was observed in 11/18 patients (median follow-up of 17 months (IQR 5-43.7 months)).

CONCLUSIONS: First-line treatment of PCNSL with the modified Bonn protocol is highly effective. The outcome compares well with other seemingly more toxic PCNSL protocols for younger patients. In patients with disease recurrence, second-line therapy according to the modified Freiburg protocol appears to be effective.

© The Author(s) 2025. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

PMID: 39902392

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