High-dose methotrexate, ibrutinib, and temozolomide in the treatment of newly diagnosed primary CNS lymphoma: a multicenter, prospective phase-II study.

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 (MIT) 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 complete response rate was 72.7% for induction therapy. The 2-year progression-free survival (PFS) and overall survival were 57.6% (95%CI: 49.0-66.2) and 84.8% (95%CI: 78.6-91.0). The incidence of grade ≧ 3 adverse events was 27.3% (10/33). Mutations in PIM1, MYD88, BTG2, and CD79B were most frequent among 475 genes tested by targeted sequencing of tumor and 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 PFS (p = 0.044).