Background: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin lymphoma that affects the brain, eyes, cerebrospinal fluid (CSF), or spinal cord without systemic involvement. Current treatments including surgery, chemotherapy and whole-brain radiotherapy often fail to achieve satisfactory effect, especially in elderly. Novel insights into the pathophysiology of PCNSL have identified key mechanisms in tumor pathogenesis including activation of the B-cell receptor pathway.Bruton’s tyrosine kinase (BTK) inhibitor zanubrutinib has been tested in clinical trials against R/R PCNSL and shows potential to be used in first-line treatment of PCNSL.
Aims: To evaluate efficacy and safety of Zanubrutinib, rituximab, methotrexate and cytarabine(ZRMA regimen) in patients with primary CNS diffuse large b cell lymphoma.
Methods: Retrospective study was done on patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and measurable disease who received ZRMA regimen in our hospital.Patients received four courses of ZRMA regimen every 21 days a cycle: Zanubrutinib 80mg twice daily, rituximab 375 mg/m(2) on days 0,methotrexate 3·5 g/m(2) on day 1 plus cytarabine 2 g/m(2) once daily on days 2. Patients with responsive were then received whole-brain radiotherapy, autologous stem cell transplantation or lenalidomide maintenance.
Results: Between Aug 18, 2020, and Feb 28, 2022, 15 enrolled patients were assessable. At median follow-up of 10 months（3-18）, patients had a complete remission rate of 93%(14/15). The median progression-free survival (PFS) and overall survival (OS) was not reached. The only two grade 3-4 adverse events were neutropenia(7%,1/15) and f infections(7%,1/15). The ZRMA regimen was well tolerated in these treatment-naïve PCNSL patients with an acceptable safety profile.
Summary/Conclusion: This retrospective study provides an evidence supporting the use of ZRMA regimen for further research in patients aged up to 70 years with newly diagnosed primary CNS lymphoma.