This is a prospective single arm,multi-center,phase 2 study,and this study is to evaluate the efficacy and safety of Orelabrutinib,Rituximab combined with high-dose Methotrexate(RMO) as first line regimens in the treatments of newly diagnosed primary central nervous system lymphoma(PCNSL).Objective response and complete response are the primary endpoint.

This is a single-arm,multicenter,phase 2 study to evaluate the efficacy and safety of Orelabrutinib,Rituximab combined with high-dose Methotrexate(RMO) as first line regimens in the treatments of newly diagnosed primary central nervous system lymphoma.The response will be evaluated every 2 cycles.Patients who achieved complete remission(CR) or partial remission(PR) will receive further treatment,and there are 6 cycles of RMO regimen for the induction.The patients with stable disease(SD) or progressed disease(PD) will withdraw from the trial and receive salvage regimens.After total 6 induction cycles,the investigators evaluate the efficiency again.After 6 cycles,the patients who receive CR or PR,can tolerate Autologous Hematopoietic Stem Cell Transplantation(AHSCT) will be candidates of high-dose chemotherapy and stem rescue.The patients who achieve CR or PR,cannot tolerate AHSCT will go to whole brain radiotherapy or Orelabrutinib maintenance.The patients with SD or PD will receive salvage regimen.

Inclusion Criteria:

• primary central nervous system diffuse large B-cell lymphoma histologically confirmed by brain biopsy;
• Aged 18-70 years
• Signature of informed consent;
• At least one measurable lesion;
• Neutropile≥1.5X109/L,Hemoglobin≥80g/L,Platelets≥75X109/L,Billrubin<2XULN,ALT<4XULN,AST4XULN
• The expected survival time is at least 3 months

Exclusion Criteria:

• Those who have contraindications to any of the components in the Orelabrutinib,Rituximab and HD-MTX
• History of other malignancies that may affect the compliance of the research protocol or the analysis of the results
• Severe cardiac insufficiency
• Other antitumor treatments were used
• Human immunodeficiency virus(HIV)antibody is positive
• Pregnant or lactating women
• Researchers consider if anyone not suitable for enrollment.