Phase II trial of hypomethylating agent combined with nivolumab for acute myeloid leukaemia relapse after allogeneic haematopoietic cell transplantation-Immune signature correlates with response.

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Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_34E444E517E5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
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.
Journal
British journal of haematology
Author(s)
Apostolova P., Kreutmair S., Toffalori C., Punta M., Unger S., Burk A.C., Wehr C., Maas-Bauer K., Melchinger W., Haring E., Hoefflin R., Shoumariyeh K., 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., Boerries M., Andrieux G., Finke J., Becher B., Vago L., Zeiser R.
ISSN
1365-2141 (Electronic)
ISSN-L
0007-1048
Publication state
Published
Issued date
10/2023
Peer-reviewed
Oui
Volume
203
Number
2
Pages
264-281
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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 <sup>+</sup> , HLA-DR <sup>+</sup> ), low senescence (KLRG1 <sup>-</sup> , CD57 <sup>-</sup> ) CD8 <sup>+</sup> 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.
Keywords
acute myeloid leukaemia, allogeneic haematopoietic cell transplantation, hypomethylating agent, immune checkpoint inhibition, immune phenotype, relapse, single-cell RNA-sequencing, single-cell immunomonitoring
Pubmed
Web of science
Open Access
Yes
Create date
07/08/2023 14:23
Last modification date
13/02/2024 7:28
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