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dc.contributor.author
Apostolova, Petya
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Kreutmair, Stefanie
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Toffalori, Cristina
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Punta, Marco
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Unger, Susanne
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Burk, Ann Cathrin
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Wehr, Claudia
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Maas Bauer, Kristina
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Melchinger, Wolfgang
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Haring, Eileen
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Höfflin, Rouven
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Shoumariyeh, Khalid
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Hupfer, Valerie
dc.contributor.author
Lauer, Eliza Maria
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Duquesne, Sandra
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Lowinus, Theresa
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Núñez, Nicolás
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Alberti, Chiara
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da Costa Pereira, Sara
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Merten, Carla Helena
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Power, Laura
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Weiss, Matthias
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Böke, Caroline
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Pfeifer, Dietmar
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Marks, Reinhard
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Bertz, Hartmut
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Wäsch, Ralph
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Ihorst, Gabriele
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Gentner, Bernhard
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Duyster, Justus
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Boerries, Melanie
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Andrieux, Geoffroy
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Finke, Juergen
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Becher, Burkhard
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Vago, Luca
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Zeiser, Robert
dc.date.available
2024-08-06T12:14:14Z
dc.date.issued
2023-10
dc.identifier.citation
Apostolova, Petya; Kreutmair, Stefanie; Toffalori, Cristina; Punta, Marco; Unger, Susanne; et al.; Phase II trial of hypomethylating agent combined with nivolumab for acute myeloid leukaemia relapse after allogeneic haematopoietic cell transplantation—Immune signature correlates with response; Wiley Blackwell Publishing, Inc; British Journal of Haematology; 203; 2; 10-2023; 264-281
dc.identifier.uri
http://hdl.handle.net/11336/241849
dc.description.abstract
Acute myeloid leukaemia (AML) relapse after allogeneic haematopoietic cell transplantation (allo-HCT) is often driven by immune-related mechanisms and associated with poor prognosis. Immune checkpoint inhibitors combined with hypomethylating agents (HMA) may restore or enhance the graft-versus-leukaemia effect. Still, data about using this combination regimen after allo-HCT are limited. We conducted a prospective, phase II, open-label, single-arm study in which we treated patients with haematological AML relapse after allo-HCT with HMA plus the anti-PD-1 antibody nivolumab. The response was correlated with DNA-, RNA- and protein-based single-cell technology assessments to identify biomarkers associated with therapeutic efficacy. Sixteen patients received a median number of 2 (range 1–7) nivolumab applications. The overall response rate (CR/PR) at day 42 was 25%, and another 25% of the patients achieved stable disease. The median overall survival was 15.6 months. High-parametric cytometry documented a higher frequency of activated (ICOS+, HLA-DR+), low senescence (KLRG1−, CD57−) CD8+ effector T cells in responders. We confirmed these findings in a preclinical model. Single-cell transcriptomics revealed a pro-inflammatory rewiring of the expression profile of T and myeloid cells in responders. In summary, the study indicates that the post-allo-HCT HMA/nivolumab combination induces anti-AML immune responses in selected patients and could be considered as a bridging approach to a second allo-HCT.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley Blackwell Publishing, Inc
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
AML
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HCT
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HMA
dc.subject.classification
Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Phase II trial of hypomethylating agent combined with nivolumab for acute myeloid leukaemia relapse after allogeneic haematopoietic cell transplantation—Immune signature correlates with response
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2024-04-09T11:42:27Z
dc.identifier.eissn
1365-2141
dc.journal.volume
203
dc.journal.number
2
dc.journal.pagination
264-281
dc.journal.pais
Reino Unido
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dc.journal.ciudad
Londres
dc.description.fil
Fil: Apostolova, Petya. Albert Ludwigs University of Freiburg; Alemania. German Cancer Research Center; Alemania
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Fil: Kreutmair, Stefanie. Universitat Zurich; Suiza. German Cancer Research Center; Alemania
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Fil: Toffalori, Cristina. Istituto di Ricovero e Cura a Carattere Scientifico; Italia
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Fil: Punta, Marco. Istituto di Ricovero e Cura a Carattere Scientifico; Italia
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Fil: Unger, Susanne. Universitat Zurich; Suiza
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Fil: Burk, Ann Cathrin. Universite de Fribourg (unifr); . German Cancer Research Center; Alemania
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Fil: Wehr, Claudia. Universite de Fribourg (unifr);
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Fil: Maas Bauer, Kristina. Universite de Fribourg (unifr);
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Fil: Melchinger, Wolfgang. Universite de Fribourg (unifr);
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Fil: Haring, Eileen. Universite de Fribourg (unifr); . German Cancer Research Center; Alemania
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Fil: Höfflin, Rouven. Universite de Fribourg (unifr);
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Fil: Shoumariyeh, Khalid. Universite de Fribourg (unifr);
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Fil: Hupfer, Valerie. Universite de Fribourg (unifr);
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Fil: Lauer, Eliza Maria. Universite de Fribourg (unifr);
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Fil: Duquesne, Sandra. Universite de Fribourg (unifr);
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Fil: Lowinus, Theresa. Universite de Fribourg (unifr);
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Fil: Núñez, Nicolás. Universitat Zurich; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
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Fil: Alberti, Chiara. Universitat Zurich; Suiza
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Fil: da Costa Pereira, Sara. Universitat Zurich; Suiza
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Fil: Merten, Carla Helena. Universitat Zurich; Suiza
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Fil: Power, Laura. Universitat Zurich; Suiza
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Fil: Weiss, Matthias. Universite de Fribourg (unifr);
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Fil: Böke, Caroline. Universite de Fribourg (unifr);
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Fil: Pfeifer, Dietmar. Universite de Fribourg (unifr);
dc.description.fil
Fil: Marks, Reinhard. Universite de Fribourg (unifr);
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Fil: Bertz, Hartmut. Universite de Fribourg (unifr);
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Fil: Wäsch, Ralph. Universite de Fribourg (unifr);
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Fil: Ihorst, Gabriele. Universite de Fribourg (unifr);
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Fil: Gentner, Bernhard. Istituto di Ricovero e Cura a Carattere Scientifico; Italia. Universite de Lausanne; Suiza
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Fil: Duyster, Justus. Universite de Fribourg (unifr);
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Fil: Boerries, Melanie. German Cancer Research Center; Alemania. Universite de Fribourg (unifr);
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Fil: Andrieux, Geoffroy. Universite de Fribourg (unifr);
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Fil: Finke, Juergen. Universite de Fribourg (unifr);
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Fil: Becher, Burkhard. Universitat Zurich; Suiza
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Fil: Vago, Luca. Istituto di Ricovero e Cura a Carattere Scientifico; Italia. Vita Salute Universidad San Raffaele; Italia
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Fil: Zeiser, Robert. German Cancer Research Center; Alemania. Universite de Fribourg (unifr);
dc.journal.title
British Journal of Haematology
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1111/bjh.19007
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1111/bjh.19007
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