Journal Article

DKFZ-2023-01580

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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, P.DKFZ* ; Kreutmair, S.DKFZ* ; Toffalori, C. ; Punta, M. ; Unger, S. ; Burk, A.-C.DKFZ* ; Wehr, C. ; Maas-Bauer, K. ; Melchinger, W. ; Haring, E.DKFZ* ; Hoefflin, R. ; Shoumariyeh, K.DKFZ* ; Hupfer, V. ; Lauer, E. M. ; Duquesne, S. ; Lowinus, T. ; Gonzalo Núñez, N. ; Alberti, C. ; da Costa Pereira, S. ; Merten, C. H. ; Power, L. ; Weiss, M. ; Böke, C. ; Pfeifer, D. ; Marks, R. ; Bertz, H. ; Wäsch, R. ; Ihorst, G. ; Gentner, B. ; Duyster, J. ; Börries, M.DKFZ* ; Andrieux, G. ; Finke, J. ; Becher, B. ; Vago, L. ; Zeiser, R.DKFZ*

2023
Wiley-Blackwell Oxford [u.a.]

This record in other databases:  

Please use a persistent id in citations: doi:10.1111/bjh.19007

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. Trial-registration: EudraCT-No. 2017-002194-18.

Keyword(s): acute myeloid leukaemia ; allogeneic haematopoietic cell transplantation ; hypomethylating agent ; immune checkpoint inhibition ; immune phenotype ; relapse ; single-cell RNA-sequencing ; single-cell immunomonitoring

Note: 2023 Oct;203(2):264-281

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Freiburg (FR01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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