Review

. 2024 Jan:196:113436.

doi: 10.1016/j.ejca.2023.113436. Epub 2023 Nov 14.

A prospective observational study of real-world treatment and outcome in secondary CNS lymphoma

Stefan Habringer¹, Uta M Demel², Anne-Katrin Fietz³, Felicitas Lammer⁴, Roland Schroers⁵, Silvia Hofer⁶, Osnat Bairey⁷, Jan Braess⁸, Anna Sofia Meier-Stiegen⁹, Reingard Stuhlmann¹⁰, Martin Schmidt-Hieber¹¹, Johannes Hoffmann¹², Bettina Zinngrebe⁹, Ulrich Kaiser¹³, Peter Reimer¹⁴, Robert Möhle¹⁵, Peter Fix¹⁶, Heinz-Gert Höffkes¹⁷, Ulrich Langenkamp¹⁸, Christian Meyer Zum Büschenfelde¹⁹, Olaf Hopfer²⁰, Andrea Stoltefuß²¹, Paul La Rosée²², Henning Blasberg²³, Karin Jordan²⁴, Stephan Kaun²⁵, Anna Meurer⁴, Meike Unteroberdörster²⁶, Ann-Christin von Brünneck²⁷, David Capper²⁸, Frank L Heppner²⁸, Björn Chapuy⁴, Martin Janz⁴, Stefan Schwartz²⁹, Frank Konietschke³, Peter Vajkoczy²⁶, Agnieszka Korfel⁴, Ulrich Keller³⁰

Affiliations

¹ Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute of Health at Charité (BIH), Berlin, Germany; German Cancer Consortium (DKTK), Berlin, Germany.
² Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute of Health at Charité (BIH), Berlin, Germany.
³ Institute of Biostatistics and Clinical Epidemiology, Charité - Universitätsmedizin, Berlin, Germany.
⁴ Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁵ Department of Medicine, Hematology and Oncology, Ruhr University Bochum, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, Germany.
⁶ Division Medical Oncology Cantonal Hospital Luzern, Luzern, Switzerland; Department of Neurology, University Hospital Zürich, Zürich, Switzerland.
⁷ Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Tel Aviv University, Tel Aviv, Israel.
⁸ Department of Oncology and Hematology, Hospital Barmherzige Brüder, Regensburg, Germany.
⁹ Department of Hematology, Oncology and Palliative Care, Department of Internal Medicine, Evangelisches Klinikum Bethel, Bielefeld, Germany.
¹⁰ Department of Hematology, Oncology and Stem Cell Transplantation, Asklepios Hospital St. Georg, Hamburg, Germany.
¹¹ Department of Hematology and Oncology, Carl-Thiem-Klinikum Cottbus, Cottbus, Germany.
¹² Pius-Hospital, University Medicine Oldenburg, Department of Hematology and Oncology, University Department Internal Medicine-Oncology, Oldenburg, Germany.
¹³ Medizinische Klinik II, St Bernward Krankenhaus, Hildesheim, Germany.
¹⁴ Department of Hematology, Medical Oncology and Stem Cell Transplantation, Kliniken Essen-Mitte, Essen, Germany.
¹⁵ Department of Internal Medicine II, Medical University Hospital, Tübingen, Germany.
¹⁶ Onkologische Praxis Dr. med. Peter Fix, Jena, Germany.
¹⁷ Klinikum Fulda, Tumorklinik, Fulda, Germany.
¹⁸ Department of Internal Medicine, Medical Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, University of Rostock, 18057 Rostock, Germany.
¹⁹ 2. Med. Klinik, ViDia Christliche Kliniken, Karlsruhe, Germany.
²⁰ Department of Medicine I, Hospital Frankfurt (Oder), Frankfurt (Oder), Germany.
²¹ Department of Hematology, Oncology and Palliative Care, Evangelisches Krankenhaus Hamm, Hamm, Germany.
²² Abteilung Hämatologie und Internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany; Klinik für Innere Medizin II, Schwarzwald-Baar-Klinikum, Villingen-Schwenningen, Germany.
²³ Hospital of Internal Medicine II, Hematology and Oncology, St. Georg Hospital Leipzig, Leipzig, Germany.
²⁴ Department of Hematology, Oncology and Palliative Medicine, Ernst von Bergmann Hospital, Potsdam, Germany.
²⁵ Hematology/Oncology, Klinikum Bremen-Mitte, Bremen, Germany.
²⁶ Department of Neurosurgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
²⁷ Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
²⁸ Department of Neuropathology, Charité - Universitätsmedizin Berlin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany; Cluster of Excellence, NeuroCure, Berlin, Germany.
²⁹ Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Cancer Consortium (DKTK), Berlin, Germany.
³⁰ Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Cancer Consortium (DKTK), Berlin, Germany. Electronic address: ulrich.keller@charite.de.

PMID: 38008033
DOI: 10.1016/j.ejca.2023.113436

Review

A prospective observational study of real-world treatment and outcome in secondary CNS lymphoma

Stefan Habringer et al. Eur J Cancer. 2024 Jan.

. 2024 Jan:196:113436.

doi: 10.1016/j.ejca.2023.113436. Epub 2023 Nov 14.

Authors

Affiliations

¹ Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute of Health at Charité (BIH), Berlin, Germany; German Cancer Consortium (DKTK), Berlin, Germany.
² Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute of Health at Charité (BIH), Berlin, Germany.
³ Institute of Biostatistics and Clinical Epidemiology, Charité - Universitätsmedizin, Berlin, Germany.
⁴ Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁵ Department of Medicine, Hematology and Oncology, Ruhr University Bochum, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, Germany.
⁶ Division Medical Oncology Cantonal Hospital Luzern, Luzern, Switzerland; Department of Neurology, University Hospital Zürich, Zürich, Switzerland.
⁷ Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Tel Aviv University, Tel Aviv, Israel.
⁸ Department of Oncology and Hematology, Hospital Barmherzige Brüder, Regensburg, Germany.
⁹ Department of Hematology, Oncology and Palliative Care, Department of Internal Medicine, Evangelisches Klinikum Bethel, Bielefeld, Germany.
¹⁰ Department of Hematology, Oncology and Stem Cell Transplantation, Asklepios Hospital St. Georg, Hamburg, Germany.
¹¹ Department of Hematology and Oncology, Carl-Thiem-Klinikum Cottbus, Cottbus, Germany.
¹² Pius-Hospital, University Medicine Oldenburg, Department of Hematology and Oncology, University Department Internal Medicine-Oncology, Oldenburg, Germany.
¹³ Medizinische Klinik II, St Bernward Krankenhaus, Hildesheim, Germany.
¹⁴ Department of Hematology, Medical Oncology and Stem Cell Transplantation, Kliniken Essen-Mitte, Essen, Germany.
¹⁵ Department of Internal Medicine II, Medical University Hospital, Tübingen, Germany.
¹⁶ Onkologische Praxis Dr. med. Peter Fix, Jena, Germany.
¹⁷ Klinikum Fulda, Tumorklinik, Fulda, Germany.
¹⁸ Department of Internal Medicine, Medical Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, University of Rostock, 18057 Rostock, Germany.
¹⁹ 2. Med. Klinik, ViDia Christliche Kliniken, Karlsruhe, Germany.
²⁰ Department of Medicine I, Hospital Frankfurt (Oder), Frankfurt (Oder), Germany.
²¹ Department of Hematology, Oncology and Palliative Care, Evangelisches Krankenhaus Hamm, Hamm, Germany.
²² Abteilung Hämatologie und Internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany; Klinik für Innere Medizin II, Schwarzwald-Baar-Klinikum, Villingen-Schwenningen, Germany.
²³ Hospital of Internal Medicine II, Hematology and Oncology, St. Georg Hospital Leipzig, Leipzig, Germany.
²⁴ Department of Hematology, Oncology and Palliative Medicine, Ernst von Bergmann Hospital, Potsdam, Germany.
²⁵ Hematology/Oncology, Klinikum Bremen-Mitte, Bremen, Germany.
²⁶ Department of Neurosurgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
²⁷ Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
²⁸ Department of Neuropathology, Charité - Universitätsmedizin Berlin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany; Cluster of Excellence, NeuroCure, Berlin, Germany.
²⁹ Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Cancer Consortium (DKTK), Berlin, Germany.
³⁰ Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Cancer Consortium (DKTK), Berlin, Germany. Electronic address: ulrich.keller@charite.de.

PMID: 38008033
DOI: 10.1016/j.ejca.2023.113436

Abstract

Background: Secondary central nervous system lymphoma (SCNSL) confers a dismal prognosis and treatment advances are constrained by the lack of prospective studies and real-world treatment evidence.

Methods: Patients with SCNSL of all entities were included at first diagnosis and patient characteristics, treatment data, and outcomes were prospectively collected in the Secondary CNS Lymphoma Registry (SCNSL-R) (NCT05114330).

Findings: 279 patients from 47 institutions were enrolled from 2011 to 2022 and 243 patients (median age: 66 years; range: 23-86) were available for analysis. Of those, 49 (20 %) patients presented with synchronous (cohort I) and 194 (80 %) with metachronous SCNSL (cohort II). The predominant histology was diffuse large B-cell lymphoma (DLBCL, 68 %). Median overall survival (OS) from diagnosis of CNS involvement was 17·2 months (95 % CI 12-27·5), with longer OS in cohort I (60·6 months, 95 % CI 45·5-not estimable (NE)) than cohort II (11·4 months, 95 % CI 7·8-17·7, log-rank test p < 0.0001). Predominant induction regimens included R-CHOP/high-dose MTX (cohort I) and high-dose MTX/cytarabine (cohort II). Rituximab was used in 166 (68 %) of B-cell lymphoma. Undergoing consolidating high-dose therapy and autologous hematopoietic stem cell transplantation (HDT-ASCT) in partial response (PR) or better was associated with longer OS (HR adjusted 0·47 (95 % CI 0·25-0·89), p = 0·0197).

Interpretation: This study is the largest prospective cohort of SCNSL patients providing a comprehensive overview of an international real-world treatment landscape and outcomes. Prognosis was better in patients with SCNSL involvement at initial diagnosis (cohort I) and consolidating HDT-ASCT was associated with favorable outcome in patients with PR or better.

Keywords: Autologous stem cell transplantation; High-dose chemotherapy; Real-world data; Registry study; SCNSL; Secondary Central Nervous System Lymphoma.

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Conflict of interest statement

Declaration of Competing Interest U.Ke. served in an advisory role for BMS/ Celgene, Takeda, Janssen, Gilead/ Kite, Roche, Abbvie, AstraZeneca, Novartis, Lilly, Pentixapharm and received travel support from BMS/ Celgene, Takeda, Janssen, Roche, Abbvie, Gilead/ Kite, AstraZeneca, Novartis, Lilly, Pentixapharm. S.H. served in an advisory role for Pentixapharm. Ro.S. served in an advisory role for BMS/ Celgene, Janssen, Gilead/ Kite, and Novartis. M.S-H. has an advisory role for Celgene GmbH, Amgen GmbH, Gilead/ Kite, Sanofi-Aventis, Glaxo Smith Kline, Bristol Myers Squibb, Shionogi and received financial support from Janssen-Cilag, Takeda, Novartis, Pfizer, Roche, Vifor Pharma, Celgene. P.L.R. received payment from Novartis, MSD, Abbvie, Roche, Incyte, Janssen-Cilag and travel support from Abbvie, Novartis, BMS, Janssen-Cilag and Roche. K.J. received royalties from Elsevier and Wolters Kluwer, obtained consulting fees and honoraria from Amgen, art tempi, Astra Zeneca, BD Solutions, Helsinn, Hexal, Karyopharm med update GmbH, MSD, Mundipharma, onkowissen, Riemser, Roche, Shire (Takeda), Vifor Pharma and Voluntis, B.C. received research grants from Gilead, received honoraria from BMS, Astra Zeneca, Gilead, Roche, Sandoz, Incyte, Abbvie and received travel support from Roche and Gilead. St. S. received research grants from Protherics Medicines Development Ltd., served in an advisory role for AMGEN, Gilead Sciences, Pfizer, SERB SAS, received honoraria from Akademie für Infektionsmedizin e.V., AMGEN, AVIR Pharma, CSi Hamburg GmbH, Gilead Sciences, Labor28, Novartis, Persberg Group GmbH/DGIM e.V., Pfizer, Vivantes GmbH and received travel support from Gilead Sciences and Novartis. A.K. Received financial support from Riemser. All remaining authors have declared no conflicts of interest.

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A prospective observational study of real-world treatment and outcome in secondary CNS lymphoma

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A prospective observational study of real-world treatment and outcome in secondary CNS lymphoma

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