Circulating Tumor DNA Sequencing for Biologic Classification and Individualized Risk Stratification in Patients With Hodgkin Lymphoma.

Autor:	Heger JM; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.; Cancer Center Cologne Essen-Partner Site Cologne, CIO Cologne, University of Cologne, Cologne, Germany.; Cologne Lymphoma Working Group (CLWG), Cologne, Germany.; Mildred Scheel School of Oncology Aachen Bonn Cologne Düsseldorf (MSSO ABCD), Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany., Mammadova L; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.; Cancer Center Cologne Essen-Partner Site Cologne, CIO Cologne, University of Cologne, Cologne, Germany.; German Hodgkin Study Group (GHSG), Cologne, Germany., Mattlener J; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.; Cancer Center Cologne Essen-Partner Site Cologne, CIO Cologne, University of Cologne, Cologne, Germany.; German Hodgkin Study Group (GHSG), Cologne, Germany., Sobesky S; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.; Cancer Center Cologne Essen-Partner Site Cologne, CIO Cologne, University of Cologne, Cologne, Germany.; German Hodgkin Study Group (GHSG), Cologne, Germany., Cirillo M; University of Western Australia and Royal Perth Hospital, Perth, Australia., Altmüller J; West German Genome Center (WGGC), University of Cologne, Cologne, Germany.; Technology Platform Genomics, Berlin Institute of Health at Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany., Kirst E; West German Genome Center (WGGC), University of Cologne, Cologne, Germany.; Hematopathology Section and Lymph Node Registry, Department of Pathology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany., Reinke S; Hematopathology Section and Lymph Node Registry, Department of Pathology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany., Klapper W; Hematopathology Section and Lymph Node Registry, Department of Pathology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany., Bröckelmann PJ; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.; Cancer Center Cologne Essen-Partner Site Cologne, CIO Cologne, University of Cologne, Cologne, Germany.; Cologne Lymphoma Working Group (CLWG), Cologne, Germany.; Mildred Scheel School of Oncology Aachen Bonn Cologne Düsseldorf (MSSO ABCD), Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.; German Hodgkin Study Group (GHSG), Cologne, Germany.; Max Planck Institute for Biology of Ageing, Cologne, Germany., Ferdinandus J; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.; Cancer Center Cologne Essen-Partner Site Cologne, CIO Cologne, University of Cologne, Cologne, Germany.; German Hodgkin Study Group (GHSG), Cologne, Germany., Kaul H; German Hodgkin Study Group (GHSG), Cologne, Germany., Schneider G; German Hodgkin Study Group (GHSG), Cologne, Germany., Schneider J; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.; Cancer Center Cologne Essen-Partner Site Cologne, CIO Cologne, University of Cologne, Cologne, Germany., Schleifenbaum JK; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.; Cancer Center Cologne Essen-Partner Site Cologne, CIO Cologne, University of Cologne, Cologne, Germany.; Cologne Lymphoma Working Group (CLWG), Cologne, Germany., Ullrich RT; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.; Cancer Center Cologne Essen-Partner Site Cologne, CIO Cologne, University of Cologne, Cologne, Germany., Freihammer M; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.; Cancer Center Cologne Essen-Partner Site Cologne, CIO Cologne, University of Cologne, Cologne, Germany., Awerkiew S; Institute for Virology, University of Cologne, Cologne, Germany., Lohmann M; German Hodgkin Study Group (GHSG), Cologne, Germany.; Department of Hematology and Stem Cell Transplantation, University Hospital Essen, University Duisburg-Essen, German Cancer Consortium (DKTK Partner Site Essen), Essen, Germany.; Cancer Center Cologne Essen-Partner Site Essen, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Klein F; Institute for Virology, University of Cologne, Cologne, Germany., Nürnberg P; West German Genome Center (WGGC), University of Cologne, Cologne, Germany., Hallek M; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.; Cancer Center Cologne Essen-Partner Site Cologne, CIO Cologne, University of Cologne, Cologne, Germany., Rossi D; Division of Hematology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.; Laboratory of Experimental Hematology, Institute of Oncology Research, Bellinzona, Switzerland., Mauz-Körholz C; Pediatric Hematology, Oncology and Immunodeficiencies, Justus-Liebig University of Giessen, Giessen, Germany.; Medical Faculty of the Martin-Luther-University of Halle, Wittenberg, Halle, Germany., Gattenlöhner S; Institute for Pathology, Justus Liebig University Giessen, Giessen, Germany., Bräuninger A; Institute for Pathology, Justus Liebig University Giessen, Giessen, Germany., Borchmann P; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.; Cancer Center Cologne Essen-Partner Site Cologne, CIO Cologne, University of Cologne, Cologne, Germany.; Cologne Lymphoma Working Group (CLWG), Cologne, Germany.; German Hodgkin Study Group (GHSG), Cologne, Germany., von Tresckow B; German Hodgkin Study Group (GHSG), Cologne, Germany.; Department of Hematology and Stem Cell Transplantation, University Hospital Essen, University Duisburg-Essen, German Cancer Consortium (DKTK Partner Site Essen), Essen, Germany.; Cancer Center Cologne Essen-Partner Site Essen, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Borchmann S; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.; Cancer Center Cologne Essen-Partner Site Cologne, CIO Cologne, University of Cologne, Cologne, Germany.; Cologne Lymphoma Working Group (CLWG), Cologne, Germany.; German Hodgkin Study Group (GHSG), Cologne, Germany.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 Dec 10; Vol. 42 (35), pp. 4218-4230. Date of Electronic Publication: 2024 Sep 30.
DOI:	10.1200/JCO.23.01867
Abstrakt:	Purpose: Current clinical challenges in Hodgkin lymphoma (HL) include difficult-to-treat relapsed/refractory disease and considerable long-term toxicities of treatment. Since clinical risk factors lack discriminatory power, intensity of therapy is mainly based on tumor burden. Exploring HL genetics and tumor microenvironment (TME) might provide valuable insights for improved risk stratification. Materials and Methods: In this study, we applied circulating tumor DNA sequencing to 243 patients obtained from pivotal German Hodgkin Study Group trials to identify subtypes of HL. Independent validation of the subtypes was performed in 96 patients treated in the EuroNet-PHL-C2 study. Outcome differences of subtypes were assessed in an event-enriched clinical validation cohort comprising 72 patients from the HD21 trial, using a refined, validated, and clinically feasible assay. Results: We propose a biologic classification of HL consisting of three distinct subtypes: inflammatory immune escape HL is characterized by frequent copy-number variations including immune escape variants such as high-level amplifications of the PD-L1 locus and an inflammatory TME. Virally-driven HL is associated with Epstein-Barr virus and/or human herpesvirus 6 and an inflammatory TME with neutrophils and macrophages, while the tumor mutational burden (TMB) is low. Oncogene-driven HL is defined by a high TMB, recurrent mutations in oncogenic drivers such as TNFAIP3 , ITPKB , and SOCS1 , and a cold TME. A refined and validated assay version aiming at clinically feasible risk stratification showed significant progression-free survival differences between subtypes. In addition, assessment of minimal residual disease (MRD) allowed for the detection of patients at very high risk of relapse within the subtypes. Conclusion: We propose a clinically feasible, noninvasive method for individualized risk stratification and MRD monitoring in patients with HL on the basis of circulating tumor DNA sequencing.
Databáze:	MEDLINE
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