Key point IRM appears promising and well tolerated as first-line therapy for newly diagnosed PCNS DLBCL in a small pilot cohort; these hypothesis-generating results require confirmation in larger prospective studies. 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).
Guo et al. (2025) studied this question.