Early mortality in atezolizumab/bevacizumab for HCC is associated with impaired liver function and alterations of systemic immunity
Although rare in clinical trial populations, early mortality (EM) is a significant concern following the initiation of immune checkpoint inhibitors in patients with hepatocellular carcinoma (HCC) in real-world cohorts, highlighting the need for adequate risk stratification and patient selection. Using data of a large, European real-world cohort as well as FACS-based immunophenotyping of baseline peripheral blood mononuclear cells, we comprehensively characterized the frequency, risk factors, and biomarkers associated with EM in atezo/bev-treated patients with HCC. We identified EM to represent a common event in patients with HCC after treatment initiation and demonstrated impaired liver function, elevated biomarkers of inflammation, and reduced lymphocyte frequencies and increased regulatory T cell activity to be associated with increased EM risk. These findings can help clinicians identify patients with HCC at high risk of EM, enabling adequate and informed decision-making regarding end-of-life care and palliative treatment.
Authors
- Friedrich Foerster (ORCID: https://orcid.org/0000-0002-3234-8891)
- Ignazio Piseddu (ORCID: https://orcid.org/0000-0001-8331-9778)
- Florian Paul Reiter (ORCID: https://orcid.org/0000-0003-3807-1456)
- Alexander B. Philipp (ORCID: https://orcid.org/0000-0002-0215-9977)
- Julia V. Mayerle (ORCID: https://orcid.org/0000-0002-3666-6459)
- Ursula Ehmer (ORCID: https://orcid.org/0000-0002-0441-1953)
- Katrin Böttcher (ORCID: https://orcid.org/0000-0002-4154-8270)
- Monika Rau (ORCID: https://orcid.org/0000-0003-1219-4044)
- Najib Ben Khaled (ORCID: https://orcid.org/0000-0002-9681-2542)
- David Anz (ORCID: https://orcid.org/0000-0002-4314-777X)
- Leonie Jochheim (ORCID: https://orcid.org/0009-0003-4522-9343)
- Monika Karin
- Matthias Thaler
- Karin Berger (ORCID: https://orcid.org/0000-0003-1768-2071)
- Andreas Thalmeier
- J. Schütte
- Osman Öcal (ORCID: https://orcid.org/0000-0001-5234-1921)
- Andreas Geier (ORCID: https://orcid.org/0000-0002-9626-5083)
- Enrico Narciso De Toni (ORCID: https://orcid.org/0000-0002-8101-8207)
- Matthias Pinter (ORCID: https://orcid.org/0000-0002-7260-532X)
- Simon Johannes Gairing (ORCID: https://orcid.org/0000-0003-3240-5152)
- Jens Ricke (ORCID: https://orcid.org/0000-0001-8762-8594)
- Marianna Alunni‐Fabbroni (ORCID: https://orcid.org/0000-0002-9710-1662)
- Alexander Weich (ORCID: https://orcid.org/0000-0002-4127-1347)
- Marino Venerito (ORCID: https://orcid.org/0000-0001-8581-0974)
- Friedrich Sinner (ORCID: https://orcid.org/0000-0003-0524-8833)
- Julia S. Schneider
- Lorenz Balcar (ORCID: https://orcid.org/0000-0002-6708-3061)
- Stefan Enßle
- Katarina Ondrejkova
- Valentina Zarka
- Christian M. Lange (ORCID: https://orcid.org/0000-0001-9983-5136)
- Christian Schulz (ORCID: https://orcid.org/0000-0003-3878-7833)
- Jan Gaertig
Institutions
- Johannes Gutenberg University Mainz (DE)
- LMU Klinikum (DE)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- German Center for Infection Research (DE)
- Universitätsklinikum Würzburg (DE)
- German Centre for Cardiovascular Research (DE)
- University Hospital Magdeburg (DE)
- University of Duisburg-Essen (DE)
- Technical University of Munich (DE)
- Medical University of Vienna (AT)
- Ludwig-Maximilians-Universität München (DE)
- Otto-von-Guericke-Universität Magdeburg (DE)
Publication Details
- Journal
- JHEP Reports
- Published
- 2025-07-05
- DOI
- https://doi.org/10.1016/j.jhepr.2025.101513
- Citations
- 2
- Primary Topic
- Colorectal Cancer Treatments and Studies
- Type
- article
- Field-Weighted Citation Impact
- 2.09