Artículo
Phase II trial of hypomethylating agent combined with nivolumab for acute myeloid leukaemia relapse after allogeneic haematopoietic cell transplantation—Immune signature correlates with response
Apostolova, Petya; Kreutmair, Stefanie; Toffalori, Cristina; Punta, Marco; Unger, Susanne; Burk, Ann Cathrin; Wehr, Claudia; Maas Bauer, Kristina; Melchinger, Wolfgang; Haring, Eileen; Höfflin, Rouven; Shoumariyeh, Khalid; Hupfer, Valerie; Lauer, Eliza Maria; Duquesne, Sandra; Lowinus, Theresa; Núñez, Nicolás
; Alberti, Chiara; da Costa Pereira, Sara; Merten, Carla Helena; Power, Laura; Weiss, Matthias; Böke, Caroline; Pfeifer, Dietmar; Marks, Reinhard; Bertz, Hartmut; Wäsch, Ralph; Ihorst, Gabriele; Gentner, Bernhard; Duyster, Justus; Boerries, Melanie; Andrieux, Geoffroy; Finke, Juergen; Becher, Burkhard; Vago, Luca; Zeiser, Robert
![Icon](/themes/CONICETDigital/images/conicet.png)
Fecha de publicación:
10/2023
Editorial:
Wiley Blackwell Publishing, Inc
Revista:
British Journal of Haematology
e-ISSN:
1365-2141
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
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Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Citación
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
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