Research Article: Ibrutinib combined with rituximab and high-dose methotrexate in newly diagnosed primary CNS diffuse large B-cell lymphoma: a pilot study with long-term follow-up
Abstract:
            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.
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.
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).
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).
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).          
Introduction:
							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.				
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