High-dose chemotherapy and autologous haematopoietic stem-cell transplantation in older, fit patients with primary diffuse large B-cell CNS lymphoma (MARTA): a single-arm, phase 2 trial.

Autor:	Schorb E; Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: elisabeth.schorb@uniklinik-freiburg.de., Isbell LK; Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Kerkhoff A; Medizinische Klinik A, Haematology and Oncology, University Hospital Muenster, Muenster, Germany., Mathas S; Charité-Universitätsmedizin Berlin, Haematology, Oncology and Cancer Immunology, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Group Biology of Malignant Lymphomas, Berlin, Germany; Experimental and Clinical Research Center, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association and Charité-Universitätsmedizin Berlin, Berlin, Germany., Braulke F; Comprehensive Cancer Center, University Medical Center Göttingen, Göttingen, Germany; Department of Haematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany., Egerer G; Department of Haematology and Oncology, Heidelberg University, Heidelberg, Germany., Röth A; Department of Haematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Schliffke S; Department of Oncology and Haematology, BMT with Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Borchmann P; Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany., Brunnberg U; Department of Internal Medicine II, Haematology and Oncology, University Hospital Frankfurt, Frankfurt, Germany., Kroschinsky F; Dresden University Hospital, Medical Department I, Dresden, Germany., Möhle R; Department of Haematology and Oncology, University of Tübingen, Tübingen, Germany., Rank A; Department of Haematology and Oncology, Augsburg Medical Center, Augsburg, Germany., Wellnitz D; Department of Internal Medicine II-Haematology and Oncology, University Clinics Schleswig Holstein-Campus Kiel, Kiel, Germany., Kasenda B; Department of Medical Oncology, University Hospital Basel, Basel, Switzerland., Pospiech L; Department of Haematology, Oncology and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany., Wendler J; Department of Haematology, Oncology and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany., Scherer F; Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Deckert M; Institute of Neuropathology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany., Henkes E; Clinic for Neuroradiology, Klinikum Stuttgart, Stuttgart, Germany., von Gottberg P; Clinic for Neuroradiology, Klinikum Stuttgart, Stuttgart, Germany., Gmehlin D; Institute for Clinical Psychology, Klinikum Stuttgart, Stuttgart, Germany., Backenstraß M; Institute for Clinical Psychology, Klinikum Stuttgart, Stuttgart, Germany., Jensch A; Stuttgart Cancer Center-Tumorzentrum Eva Mayr-Stihl, Klinikum Stuttgart, Stuttgart, Germany., Burger-Martin E; Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Clinical Trials Unit, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Grishina O; Clinical Trials Unit, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Fricker H; Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Malenica N; Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Orbán A; Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Duyster J; Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Ihorst G; Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Clinical Trials Unit, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Finke J; Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Illerhaus G; Department of Haematology, Oncology and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany.
Jazyk:	angličtina
Zdroj:	The Lancet. Haematology [Lancet Haematol] 2024 Mar; Vol. 11 (3), pp. e196-e205. Date of Electronic Publication: 2024 Jan 29.
DOI:	10.1016/S2352-3026(23)00371-X
Abstrakt:	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.)
Databáze:	MEDLINE
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