% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Apostolova:277924, author = {P. Apostolova$^*$ and S. Kreutmair$^*$ and C. Toffalori and M. Punta and S. Unger and A.-C. Burk$^*$ and C. Wehr and K. Maas-Bauer and W. Melchinger and E. Haring$^*$ and R. Hoefflin and K. Shoumariyeh$^*$ and V. Hupfer and E. M. Lauer and S. Duquesne and T. Lowinus and N. Gonzalo Núñez and C. Alberti and S. da Costa Pereira and C. H. Merten and L. Power and M. Weiss and C. Böke and D. Pfeifer and R. Marks and H. Bertz and R. Wäsch and G. Ihorst and B. Gentner and J. Duyster and M. Börries$^*$ and G. Andrieux and J. Finke and B. Becher and L. Vago and R. Zeiser$^*$}, title = {{P}hase {II} trial of hypomethylating agent combined with nivolumab for acute myeloid leukaemia relapse after allogeneic haematopoietic cell transplantation-{I}mmune signature correlates with response.}, journal = {British journal of haematology}, volume = {203}, number = {2}, issn = {0007-1048}, address = {Oxford [u.a.]}, publisher = {Wiley-Blackwell}, reportid = {DKFZ-2023-01580}, pages = {264-281}, year = {2023}, note = {2023 Oct;203(2):264-281}, 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.}, keywords = {acute myeloid leukaemia (Other) / allogeneic haematopoietic cell transplantation (Other) / hypomethylating agent (Other) / immune checkpoint inhibition (Other) / immune phenotype (Other) / relapse (Other) / single-cell RNA-sequencing (Other) / single-cell immunomonitoring (Other)}, cin = {FR01}, ddc = {610}, cid = {I:(DE-He78)FR01-20160331}, pnm = {899 - ohne Topic (POF4-899)}, pid = {G:(DE-HGF)POF4-899}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:37539479}, doi = {10.1111/bjh.19007}, url = {https://inrepo02.dkfz.de/record/277924}, }