OptiMATe: De-escalated Induction Treatment in Primary CNS Lymphoma

Inclusion Criteria: 1. Immunocompetent patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system (PCNSL). 2. Male or female patients aged 18-65 years irrespective of ECOG or 66-70 years with ECOG Performance Status ≤2. 3. Histologically or cytologically assessed diagnosis of B-cell lymphoma by local pathologist. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy. 4. Disease exclusively located in the CNS. 5. At least one measurable lesion. 6. Previously untreated patients (previous or ongoing steroid treatment admitted) 7. Negative pregnancy test 8. Written informed consent obtained according to international guidelines and local laws by patient or authorized legal representative in case patient is temporarily legally not competent due to his or her disease. 9. Ability to understand the nature of the trial and the trial related procedures and to comply with them. Exclusion Criteria: 1. Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation. 2. Systemic lymphoma manifestation (outside the CNS). 3. Primary vitreoretinal lymphoma without manifestation in the brain parenchyma or spinal cord 4. Previous or concurrent malignancies with the exception of surgically cured carcinoma in situ of the cervix, carcinoma of the skin or other kinds of cancer without evidence of disease for at least 5 years. 5. Previous Non-Hodgkin lymphoma at any time. 6. Inadequate renal function (clearance \< 60 ml/min). 7. Inadequate bone marrow, cardiac, pulmonary or hepatic function according to investigator´s decision 8. Active hepatitis B or C disease. 9. Concurrent treatment with other experimental drugs or participation in an interventional clinical trial with study medication being administered within the last 30 days before the start of this study. 10. Third space fluid accumulation \> 500 ml. 11. Hypersensitivity to study treatment or any component of the formulation. 12. Taking any medications that are likely to cause interactions with the study medication 13. Known or persistent abuse of medication, drugs or alcohol. 14. Active COVID-19-infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic 15. Patients without legal capacity who are unable to understand the nature, significance and consequences of the trial and without designated legal representative. 16. Previous participation in this trial. 17. Persons who are in a relationship of dependency/employment with the sponsor and/or the investigator. 18. Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule 19. Current or planned pregnancy, nursing period 20. For fertile patients: Failure to use one of the following safe methods of contraception: intra-uterine device or hormonal contraception in combination with a mechanical method of contraception.