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Background: Available treatments for older patients with primary diffuse large B-cell CNS lymphoma (PCNSL) offer progression-free survival of up to 16 months. We aimed to investigate an intensified treatment of high-dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT) in older patients with PCNSL., Methods: MARTA was a prospective, single-arm, phase 2 study done at 15 research hospitals in Germany. Patients aged 65 years or older with newly diagnosed, untreated PCNSL were enrolled if they had an Eastern Cooperative Oncology Group performance status of 0-2 and were fit for high-dose chemotherapy and autologous HSCT. Induction treatment consisted of two 21-day cycles of high-dose intravenous methotrexate 3·5 g/m 2 (day 1), intravenous cytarabine 2 g/m 2 twice daily (days 2 and 3), and intravenous rituximab 375 mg/m 2 (days 0 and 4) followed by high-dose chemotherapy with intravenous rituximab 375 mg/m 2 (day -8), intravenous busulfan 3·2 mg/kg (days -7 and -6), and intravenous thiotepa 5 mg/kg (days -5 and -4) plus autologous HSCT. The primary endpoint was progression-free survival at 12 months in all patients who met eligibility criteria and started treatment. The study was registered with the German clinical trial registry, DRKS00011932, and recruitment is complete., Findings: Between Nov 28, 2017, and Sept 16, 2020, 54 patients started induction treatment and 51 were included in the full analysis set. Median age was 71 years (IQR 68-75); 27 (53%) patients were female and 24 (47%) were male. At a median follow-up of 23·0 months (IQR 16·8-37·4), 23 (45%) of 51 patients progressed, relapsed, or died. 12-month progression-free survival was 58·8% (80% CI 48·9-68·2; 95% CI 44·1-70·9). During induction treatment, the most common grade 3-5 toxicities were thrombocytopenia and leukopenia (each in 52 [96%] of 54 patients). During high-dose chemotherapy and autologous HSCT, the most common grade 3-5 toxicity was leukopenia (37 [100%] of 37 patients). Treatment-related deaths were reported in three (6%) of 54 patients, all due to infectious complications., Interpretation: Although the primary efficacy threshold was not met, short induction followed by high-dose chemotherapy and autologous HSCT is active in selected older patients with PCNSL and could serve as a benchmark for comparative trials., Funding: Else Kröner-Fresenius Foundation, Riemser Pharma, and Medical Center-University of Freiburg., Competing Interests: Declaration of interests ES received research funding to her institution from the Else Kröner-Fresenius Foundation, Riemser Pharma, Roche Pharma, and Bundesministerium für Bildung und Forschung Germany; received honoraria for lectures from Riemser Pharma and SERB SAS Pharmaceuticals; is on the advisory board for SERB SAS Pharmaceuticals; and is an unpaid member of the steering committee of the German Lymphoma Alliance. AK received honoraria from Roche, Celgene, Sobi, AbbVie, Takeda, and Bristol Myers Squibb; and support for attending meetings or travel from AbbVie, BeiGene, ENSA Pharma, Sobi, and Takeda. ARö received honoraria from Alexion, Amgen, Apellis, Novartis, Roche, Sanofi, and Sobi, and support for attending meetings or travel from Sobi; and is on a data safety monitoring board or advisory board from Alexion, Amgen, Apellis, Novartis, Roche, Bioverativ, Sanofi, Sobi, and Samsung. BK received consulting fees from Dayton Therapeutics and Incyte and honoraria from Dayton Therapeutics, Incyte, and Roche. LP received travel support from Medac and Gilead. JW is an unpaid member of the steering committee of the German Lymphoma Alliance. FS received research funding from Roche Sequencing Solutions, Gilead, and Takeda, and honoraria from AstraZeneca. GIh is part of the data safety monitoring board for Novartis trials. EB-M and HF received institutional research funding from the Else Kröner-Fresenius Foundation and Riemser Pharma. AO received honoraria for presentation from SERB SAS Pharmaceuticals. JF received honoraria from Medac, Neovii, and Riemser; payment for expert testimony from Sanofi; and support for attending meetings or travel from Medac and Neovii. GIl received research funding from Bundesministerium für Bildung und Forschung Germany; honoraria from Roche, Gilead, and Incyte; support for attending meetings or travel from Roche, Janssen, and Lilly; and is on an advisory board for Miltenyi Biotec. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: High-dose methotrexate-based chemotherapy is standard for primary CNS lymphoma, but most patients relapse. High-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is supposed to overcome the blood-brain barrier and eliminate residual disease in the CNS. We aimed to investigate the safety and efficacy of HCT-ASCT in patients with newly diagnosed primary CNS lymphoma., Methods: In this prospective, single-arm, phase 2 trial, we recruited patients aged 18-65 years with newly diagnosed primary CNS lymphoma and immunocompetence, with no limitation on clinical performance status, from 15 hospitals in Germany. Patients received five courses of intravenous rituximab 375 mg/m(2) (7 days before first high-dose methotrexate course and then every 10 days) and four courses of intravenous high-dose methotrexate 8000 mg/m(2) (every 10 days) and then two courses of intravenous rituximab 375 mg/m(2) (day 1), cytarabine 3 g/m(2) (days 2 and 3), and thiotepa 40 mg/m(2) (day 3). 3 weeks after the last course, patients commenced intravenous HCT-ASCT (rituximab 375 mg/m(2) [day 1], carmustine 400 mg/m(2) [day 2], thiotepa 2 × 5 mg/kg [days 3 and 4], and infusion of stem cells [day 7]), irrespective of response status after induction. We restricted radiotherapy to patients without complete response after HCT-ASCT. The primary endpoint was complete response at day 30 after HCT-ASCT in all registered eligible patients who received at least 1 day of study treatment. This trial is registered at ClinicalTrials.gov, number NCT00647049., Findings: Between Jan 18, 2007, and May 23, 2011, we recruited 81 patients, of whom two (2%) were excluded, therefore we included 79 (98%) patients in the analysis. All patients started induction treatment; 73 (92%) commenced HCT-ASCT. 61 (77·2% [95% CI 66·1-86·6]) patients achieved a complete response. During induction treatment, the most common grade 3 toxicity was anaemia (37 [47%]) and the most common grade 4 toxicity was thrombocytopenia (50 [63%]). During HCT-ASCT, the most common grade 3 toxicity was fever (50 [68%] of 73) and the most common grade 4 toxicity was leucopenia (68 [93%] of 73). We recorded four (5%) treatment-related deaths (three [4%] during induction and one [1%] 4 weeks after HCT-ASCT)., Interpretation: HCT-ASCT with thiotepa and carmustine is an effective treatment option in young patients with newly diagnosed primary CNS lymphoma, but further comparative studies are needed., Funding: University Hospital Freiburg and Amgen., (Copyright © 2016 Elsevier Ltd. All rights reserved.)