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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State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
State: Public
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
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
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