It is a single arm, multicenter, phase 2 study to explore the efficacy and safety study of R2-MTX chemotherapy（Lenalidomide, Rituximab and Methotrexate）as first-line regimens in the treatment of newly diagnosed primary central nervous system lymphoma. Objective response rate is the primary endpoint.

This is a single arm, multicenter, phase 2 study designed to evaluate the efficacy and safety of rituximab, methotrexate and lenalidomide as first-line regimens in the treatment of newly primary central nervous system lymphoma. A total of 40 patients plan to participate in this study to receive a total 6 cycles of induction chemotherapy followed by 4 cycles of maintenance chemotherapy. Follow-ups should be taken up to the first 3 years. The primary endpoint is objective response rate (ORR) and secondary endpoint includes Progression free survival (PFS), overall survival (OS), and adverse events.

Inclusion Criteria:

1. Histologically confirmed Primary Central Nervous System (CNS) lymphoma
2. Age range 18-75 years old.
3. Eastern Cooperative Oncology Group performance status 0 to 3.
4. Previously untreated. Patients treated with steroid alone are eligible.
5. Patient's who are not planned to undergo consolidation with autologous hematopoietic stem cell transplantation（HSCT）.
6. Measurable disease was defined as at least ≥1.0cm in short-diameter by MRI.
7. Life expectancy of ≥ 3 months (in the opinion of the investigator).
8. Participants must be able to understand and be willing to sign a written informed consent document.
9. Women of reproductive potential must agree to use highly effective methods of birth control during the period of therapy and for 6 months after the last dose of the study drug. Men who are sexually active must agree to use highly effective contraception during the period of therapy and for 6 months after the last dose.
10. Women of childbearing potential must have a negative plasma pregnancy test upon study entry.
11. Adequate renal function: Estimated glomerular filtration rate (GFR) or estimated creatinine clearance (CrCl) ≥ 50 mL/min;Serum creatinine ≤ 2 times the upper limit of normal.
12. Adequate liver functions: Transaminase (AST/ALT) < 3 X upper normal value & Bilirubin < 2 X upper normal value.
13. Adequate hematological function: hemoglobin ≥ 9 g/dL absolute neutrophil count (ANC) ≥ 1,500/μL and platelet count ≥ 75,000/μL.

Exclusion Criteria:

1. Patient with systemic, non-CNS lymphoma metastatic to the CNS.
2. Patient is concurrently using other approved or investigational antineoplastic agents.
3. Presence of active hepatitis B virus(HBV) infection (HBsAg positive and HBV-DNA≥ 104), hepatitis C virus(HCV) infection, acquired and congenital immunodeficiency diseases include but not limited to HIV.
4. Patient is allergic to components of the study drug.
5. Patient has an active concurrent malignancy requiring active therapy.
6. Patient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, uncontrolled congestive heart failure, uncontrolled hypertension, valvular disease, pericarditis, or myocardial infarction within 6 months of screening.
7. Patient is known to have an uncontrolled active systemic infection.
8. Patient has a life-threatening illness, medical condition, or organ system dysfunction that, in the opinion of the investigator, could compromise the subject's safety or put the study outcomes at undue risk.
9. Women who are pregnant or nursing (lactating), where pregnancy is defined as a state of a female after conception until the termination of gestation, confirmed by a positive plasma human chorionic gonadotropin(hCG) laboratory test of > 5 mIU/mL.
10. The patient is unwell or unable to participate in all required study evaluations and procedures.
11. Drug abuse, medical, psychological or social conditions which may interfering with subjects' participation in the study or evaluation of the results.
12. Patients considered unsuitable to participate in the study by the researchers.