Methotrexate, Tafasitamab, Lenalidomide and Rituximab in Patients With PCNSL

Inclusion Criteria: 1. Age 18-69 years with ECOG PS ≥2 or age ≥70 years, and ineligible for HCT-ASCT as per investigators discretion 2. Previously untreated, histologically (or cytologically) confirmed diagnosis of primary B-cell lymphoma of the central nervous system (PCNSL) by local pathologist. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy 3. At least one measurable lesion 4. Adequate organ function: * Adequate kidney function, defined as: * Serum creatinine estimated glomerular filtration rate (MDRD) ≥ 50 ml/min * Adequate hepatic function, defined as: * ALAT and ASAT ≤ 3 ULN * Bilirubin ≤ 2.0 mg/dl (except for Meulengracht disease) * Adequate bone marrow function, defined as: * White blood cell (WBC) count ≥ 3000/µL or absolute neutrophil count (ANC) ≥ 1000/µL * Platelets ≥ 50.000/µL * Hemoglobin \> 8.0 g/dl * Adequate cardiac function, defined as: * Cardiac ejection fraction ≥ 40% * Adequate pulmonary function as per investigators discretion 5. Written, signed, and dated informed consent for the trial provided by the participant 6. Female persons are eligible to participate if they are post-menopausal or females of no childbearing potential or if they agree to use a method of contraception considered safe described in Section 12.1.2.1. 7. Male persons with female partners of childbearing potential are eligible to participate if they agree to contraceptive methods as described in Section 12.1.2.2. Exclusion Criteria: 1. Prior treatment for PCNSL with the exception of a pre-phase treatment comprising steroid treatment and / or single application of rituximab 375 mg/m² and methotrexate 3.5 g/m² 2. Systemic lymphoma manifestation outside the CNS 3. Diagnosis of previous Non-Hodgkin lymphoma at any time 4. Primary vitreoretinal or leptomeningeal lymphoma without manifestation in the brain parenchyma or spinal cord 5. HIV infection of any stage as determined by presence of anti-HIV antibodies (confirmatory test) and / or presence of RNA confirmed by PCR 6. Previous or concurrent malignancies with the following exceptions: * Surgically cured carcinoma in-situ * Other kinds of cancer without evidence of disease for at least 5 years 7. Hypersensitivity to study treatment or any component of the formulation 8. Stomatitis or gastrointestinal ulcerations preventing the use of methotrexate 9. Hepatitis B, hepatitis C or hepatitis E infection as determined by PCR 10. Severe active infection 11. Congenital or acquired immunodeficiency including previous organ transplantation 12. Pregnant or nursing (lactating) women. 13. Lack of accountability and inability to appreciate the nature, meaning and consequences of the trial and to formulate their own wishes correspondingly 14. Non-compliance, for reasons including, but not limited to the following: 1. Increased alcohol consumption, drug dependency or substance abuse that would interfere with cooperation with requirements of the trial 2. Refusal of blood products during treatment 3. Any similar circumstances that appear to make protocol treatment or long-term follow-up impossible 15. Relationship of dependence or employer-employee relationship to the sponsor or the investigator