1031P - The EUROSKI Biomarker Study: Analyzing the mechanisms of treatment-free remission in chronic myeloid leukemia.

Date 09 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cancer in Adolescents
Leukaemia
Haematologic Malignancies
Presenter Sébastien Rinaldetti
Citation Annals of Oncology (2017) 28 (suppl_5): v355-v371. 10.1093/annonc/mdx373
Authors S. Rinaldetti1, C. Sticht2, M. Pfirrmann3, D. Nowak1, A. Fabarius1, W. Seifarth1, B. Spiess1, P. Panayiotidis4, M. Pagoni5, M. Dimou5, J. Dengler6, C.F. Waller7, T.H. Brümmendorf8, A. Burchert9, G. Freunek10, W. Hofmann1, F. Mahon11, S. Saussele1
  • 1Iii. Medizinische Klinik, Medizinische Fakultät Mannheim, Universität Heidelberg, 68167 - Mannheim/DE
  • 2Zentrum Für Medizinische Forschung, Medizinische Fakultät Mannheim, Universität Heidelberg, 68167 - Mannheim/DE
  • 3Institut Für Medizinische Informationsverarbeitung, Biometrie Und Epidemiologie (ibe), Ludwig-Maximilians-Universität München, Munich/DE
  • 4Molecular Hematology Laboratory, 1st Department Of Propaedeutic Medicine, National and Kapodistrian University of Athens, School of Medicine, Laikon General Hospital, Athens/GR
  • 5Of Hematology, Hellenic Society, Athens/GR
  • 6Internistische Hämatologie Und Onkologie, Onkologische Praxis Heilbronn,, Heilbronn/DE
  • 7Klinik Für Innere Medizin I, Universitätsklinikum Freiburg, Freiburg/DE
  • 8Med. Klinik Iv, Uniklinik RWTH Aachen, Aachen/DE
  • 9Klinik Für Hämatologie, Onkologie Und Immunologie, Universitätsklinikum Gießen und Marburg, Marburg/DE
  • 10Medizinisches Versorgungszentrum, Klinikum Straubing,, Straubing/DE
  • 11Institut Bergonié, University Bordeaux, Bordeaux/FR

Abstract

Background

A substantial proportion of chronic myeloid leukemia (CML) patients in deep molecular response (DMR) reach treatment-free remission (TFR) after tyrosine kinase inhibitors (TKI) cessation. The aim of this study is to identify a gene signature predictive for TFR using whole transcriptome expression analyses.

Methods

RNA from peripheral blood (PB) leukocytes of 60 CML patients who stopped TKI therapy within the EUROSKI study and 10 healthy controls were isolated. CML patients were divided into two groups of whom n = 30 patients had ongoing TFR, while 30 patients encountered molecular recurrence. RNA was isolated at the last day of TKI intake. In order to investigate differentially expressed genes, whole transcriptome arrays (Clariom D, Affymetrix) were analyzed. Candidate biomarkers were tested in multivariate analyses and gene set enrichment analyses (GSEA).

Results

CML patients in DMR compared to healthy controls showed 16000 differentially expressed genes (p  8-fold) for CML patients versus healthy controls. Significant enrichment of NFκB mediated TNFα and TGFβ pathways (FDR

Conclusions

CML patients in DMR present a considerable inflammatory gene expression pattern in PB leukocytes in contrast to healthy controls. Alike previous studies, genes involved in immune exhaustion and immune surveillance were differentially expressed between patients with TFR and relapse. The specific inflammatory gene signature of the relapse cohort suggests ‘stemness’ as third mechanism and driver for relapse.

Clinical trial identification

Legal entity responsible for the study

University Heidelberg

Funding

ELN Foundation

Disclosure

R. Sébastien: Novartis research fund. S. Saussele: Advisory board: Novartis, Bristol-Myers Squib, Pfizer and ARIAD Fees: Novartis, Bristol-Myers Squib, Pfizer and ARIAD Research grant: Novartis and Bristol-Myers Squib Travel grant: Novartis and Bristol-Myers Squib. All other authors have declared no conflicts of interest.