Primary central nervous system lymphomas (PCNSL) are rare malignancies with poor survival outcomes. The IELSG32 trial demonstrated efficacy of MATRix chemoimmunotherapy followed by autologous stem cell transplantation (auto-SCT) in PCNSL patients aged ≤ 70 years with a performance status (PS) ECOG ≤ 3. However, long-term real-world results of MATRix/auto-SCT therapy remain limited. This analysis, with a median follow-up of 52 months, aimed to evaluate the outcomes of MATRix-treated PCNSL patients in clinical practice. From 2015 to 2022, 280 PCNSL patients who received systemic therapy were identified in the NiHiL project (NCT03199066). Eighty-eight individuals treated with MATRix entered the analysis. Endpoints included efficacy and safety of induction and consolidation therapy. Seventy-eight patients who met key IELSG32 inclusion criteria (age ≤ 65 years and PS ECOG ≤ 3, or age 66-70 years and PS ECOG ≤ 2) achieved an overall response rate of 82% (complete remission rate 58%) following MATRix regimen. After median follow-up of 52 months, 4-year progression-free survival and overall survival (OS) rates were 53% and 55%, respectively. Forty-six (59%) patients completed MATRix treatment, and 32 (41%) discontinued induction therapy (15 toxicity, 11 infections, 5 progressive diseases, 1 refusal). The treatment-related mortality was 8%. Among 67 patients with responsive/stable disease, 50 underwent consolidation with whole-brain radiotherapy (WBRT, n = 13) or auto-SCT (n = 37). No significant survival differences were observed between WBRT and auto-SCT (4-year OS 84% vs. 74%, HR 0.61, 95% CI 0.16-2.29, p = 0.467). Long-term real-world outcomes of MATRix/auto-SCT therapy are comparable to IELSG32, supporting its use in younger, fit PCNSL patients. CLINICAL TRIAL REGISTRATION: The data in this analysis were collected in the observational Czech non-Hodgkin lymphoma registry "NiHiL" (NCT03199066).

1st Department of Medicine 1st Faculty of Medicine Charles University General Hospital Prague Czech Republic

4th Department of Internal Medicine Hematology Faculty of Medicine Charles University and University Hospital Hradec Kralove Hradec Králové Czech Republic

Datacenter Czech Lymphoma Study Group Prague Czech Republic

Department of Haemato Oncology Faculty of Medicine and Dentistry Palacky University and University Hospital Olomouc Czech Republic

Department of Haematology and Oncology Faculty of Medicine Charles University and University Hospital Pilsen Pilsen Czech Republic

Department of Hematology 3rd Faculty of Medicine Charles University and University Hospital Kralovske Vinohrady Prague Czech Republic

Department of Hematology and Oncology Faculty of Medicine Masaryk University and University Hospital Brno Czech Republic

Department of Hematology Medical Faculty of the Ostrava University and University Hospital Ostrava Czech Republic

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NCT03199066