{"doi":"10.1002/hon.3163_15","title":"CONSOLIDATIVE HCT‐ASCT IS SUPERIOR TO NON‐MYELOABLATIVE CHEMO‐IMMUNOTHERAPY IN NEWLY‐DIAGNOSED PCNSL ‐ UPDATED RESULTS OF THE RANDOMIZED PHASE III MATRIX/IELSG43 TRIAL","abstract":"Background: Current treatment options for patients with primary central nervous system lymphoma (PCNSL) eligible for intensive treatment approaches comprise high-dose methotrexate (HD-MTX) based immuno-chemotherapy (IT) followed by consolidating high-dose chemotherapy and ASCT (HDC-ASCT). To clarify, whether minimal residual disease may also be eliminated by non-myeloablative IT, comprising non-cross resistant cytotoxic agents, the MATRix/IELSG43 trial, an international randomised phase III trial comparing HDC-ASCT with non-myeloablative consolidation in patients with newly diagnosed PCNSL (NCT02531841) was conducted. This is an updated report on the main study endpoints. Methods: This randomized phase III trial was conducted in 79 centers in five countries. Immuno-competent patients with untreated PCNSL, aged 18–65 years irrespective of ECOG PS or 66–70 years with ECOG PS ≤ 2 were considered eligible. Induction comprised four cycles MATRix (rituximab 375 mg/m2/d days(d) 0,5; methotrexate 3.5 g/m2 d1; cytarabine 2 × 2 g/m2/d d2,3; thiotepa 30 mg/m2 d4, every three weeks. Stem cell harvest following cycle 2. Randomization was performed for patients achieving at least partial response (PR) following induction therapy. Arm A consisted of two cycles R-DeVIC (375 mg/m2 d0; dexamethasone 40 mg/d d1–3; etoposide 100 mg/m2/d d1–3; ifosfamide 1500 mg/m2/d d1–3; carboplatin 300 mg/m2 d1); Arm B, consisted of HDC-ASCT (BCNU 400 mg/m2 (d-6) and thiotepa 2 × 5 mg/kg/d d-5,-4)). The primary endpoint progression-free survival (PFS) was analyzed with a Cox proportional hazards model. Results: 368 pts were registered between July 2014 and August 2019, 230/346 pts (67%) were randomly assigned to arm A and arm B, respectively. 116 patients discontinued induction treatment, mainly due to toxicity (15%) or progressive disease (12%). Median age of the randomized pts was 59 years (range 21–70) with 22% being ≥65 years. Overall response rate (ORR) following induction treatment was 69% (52% PR, 27% CR). Thirteen pts died due to treatment-related toxicity, comprising mainly infectious complications. Following consolidation CR rate increased substantially to 65% in arm A and 68% in arm B. Six patients died of toxicity during consolidation treatment (2 in arm A and 4 in arm B), Median follow-up was 45 months (range 0.2–86). The 3-year PFS and OS rates were 79% (95% CI 71–86) and 86% (95% CI 78–91) following HDC-ASCT and 53% (95% CI 44–62%) and 71% (95% CI 61–78) after R-DeVIC (HR 0.41; p = 0.0002). The evaluation of neurocognitive functions showed no difference between arms. The research was funded by: Riemser, Roche Keywords: aggressive B-cell non-Hodgkin lymphoma, stem cell transplant Conflicts of interests pertinent to the abstract G. Illerhaus Consultant or advisory role: Roche, Gilead, Incyte Educational grants: Roche, Gilead","journal":"Hematological Oncology","year":2023,"id":371247,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.944,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":374511,"name":"Andrés J.M. 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