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Data from High-Dose Methotrexate, Ibrutinib, and Temozolomide in the Treatment of Newly Diagnosed Primary CNS Lymphoma: A Multicenter, Prospective Phase II Study

Posted on 2025-05-05 - 07:20
Abstract

Genetic alterations of chronic active B-cell receptor signaling often occur in primary central nervous system lymphoma (PCNSL). We conducted a phase II trial of high-dose methotrexate plus ibrutinib and temozolomide in the treatment of newly diagnosed PCNSL. A total of 35 patients were enrolled, with 33 patients included in the analysis. The best overall response rate was 93.9%, and the complete response rate was 72.7% for induction therapy. The 2-year progression-free survival and overall survival were 57.6% (95% confidence interval, 49.0%–66.2%) and 84.8% (95% confidence interval, 78.6%–91.0%). The incidence of grade ≥ 3 adverse events was 27.3% (10 of 33). Mutations in PIM1, MYD88, BTG2, and CD79B were most frequent among 475 genes tested by targeted sequencing of tumor and cerebrospinal fluid (CSF) samples at baseline. The consistency of ctDNA clearance from CSF/plasma and complete response on imaging were observed. Patients with clearance of ctDNA from CSF after two cycles achieved longer progression-free survival (P = 0.044).

Significance:

We report promising efficacy and good tolerability of Bruton tyrosine kinase (BTK) inhibitor ibrutinib in treatment of newly diagnosed PCNSL. Additionally, we explored the contribution of ctDNA profiling to predictive potential in this prospective study. The consistency of ctDNA clearance from CSF/plasma was associated with more sustained treatment response and survival.

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FUNDING

National Natural Science Foundation of China (NSFC)

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