Adjusted High-dose Chemotherapy with Autologous Stem Cell Transplant Vs. Conventional Immunochemotherapy in Elderly PCNSL Patients

Inclusion Criteria:

1. Immunocompetent patients with newly-diagnosed primary DLBCL of the central nervoussystem.

2. Age > 70 years or age 65-70 years if not eligible for more intensive treatment (e.g.OptiMATe trial).

3. Histologically or cytologically assessed diagnosis of B-cell lymphoma by localpathologist.

4. Diagnostic sample obtained by stereotactic or surgical biopsy, cerebrospinal fluid (CSF) cytology examination or vitrectomy.

5. Disease exclusively located in the CNS.

6. At least 1 measurable lesion.

7. Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS) ≤ 2. ECOG PS > 2accepted if due to PCNSL symptoms.

8. Patients possibly eligible for HCT-ASCT as judged by the treating physician.

9. Written informed consent obtained according to international guidelines and locallaws by patient or authorized legal representative in case patient is temporarilylegally not competent due to his or her disease.

Additional randomization criteria:

1. Patients eligible for HCT-ASCT defined by the EBL score (at most one of the 3following conditions may apply: ECOG PS > 1, Barthel Index of activities of dailyliving (ADL) < 20 and Lachs geriatric screening > 3), improvement of PS afterpre-phase treatment or clinical judgement by the treating physician after discussionwith the study expert team.

2. No evidence of disease progression after pre-phase treatment.

Exclusion Criteria:

1. Congenital or acquired immunodeficiency including HIV infection and previous organtransplantation.

2. Systemic lymphoma manifestation (outside the CNS).

3. Primary vitreoretinal lymphoma or primary leptomeningeal lymphoma withoutmanifestation in the brain parenchyma or spinal cord.

4. Previous or concurrent malignancies with the exception of surgically cured carcinomain situ or other kinds of cancer without evidence of disease for at least 5 years.

5. Previous systemic Non-Hodgkin lymphoma at any time.

6. Inadequate renal function (creatinine clearance <60 ml/min).

7. Inadequate bone marrow, cardiac, pulmonary or hepatic function according toinvestigator´s decision.

8. Active hepatitis B or C disease.

9. Concurrent treatment with other experimental drugs or participation in aninterventional clinical trial with administration of study medication within thelast thirty 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 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 measuresregarding the COVID-19 pandemic.

15. Patients without legal capacity and who are unable to understand the nature,significance and consequences of the study and without designated legalrepresentative.

16. Previous participation in this trial.

17. Persons who are in a relationship of dependency/employment to the sponsor and/ orinvestigator.

18. Any familial, sociological or geographical condition potentially hamperingcompliance with the study protocol and follow-up schedule.

19. Fertile patients refusing to use safe contraceptive methods during the study.