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Hamostaseologie 2025; 45(02): 175-187
DOI: 10.1055/a-2528-5071
Review Article

Checkpoint Inhibitors, CAR T Cells, and the Hemostatic System: What Do We Know So Far?

Christina C. Rolling
1   Department of Oncology, Hematology and BMT with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Samuel Lewirt
1   Department of Oncology, Hematology and BMT with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Antonia Beitzen-Heineke
1   Department of Oncology, Hematology and BMT with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
2   Department of Medicine, New York University Grossman School of Medicine, New York, New York, United States
,
Lennart Beckmann
1   Department of Oncology, Hematology and BMT with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Carsten Bokemeyer
1   Department of Oncology, Hematology and BMT with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Winfried Alsdorf
1   Department of Oncology, Hematology and BMT with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Minna Voigtlaender
1   Department of Oncology, Hematology and BMT with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Florian Langer
1   Department of Oncology, Hematology and BMT with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
› Institutsangaben Funding CCR is supported by the Margarete Clemens Stiftung (Deutsches Stiftungszentrum Essen) and by the Mildred Scheel Nachwuchszentrum (MSNZ) Hamburg.
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Abstract

Immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cells are novel therapeutic strategies that enhance anticancer immunity by activating or engineering cancer-targeting T cells. The resulting hyperinflammation carries several side effects, ranging from autoimmune-like symptoms to cytokine release syndrome (CRS), with potentially severe consequences. Recent findings indicate that ICIs increase the risk of venous and arterial thromboembolic adverse events. Patients with prior VTE might be at higher risk of developing new events under ICI while other risk factors vary across studies. So far, data on CAR T-linked coagulopathies are limited. Hypofibrinogenemia in the presence of CRS is the most commonly observed dysregulation of hemostatic parameters. A rare but particularly severe adverse event is the development of disseminated intravascular coagulation activation, which can occur in the setting of CRS and may be linked to immune effector cell-associated hemophagocytic lymphohistiocytosis. While the increasing number of studies on thromboembolic complications and coagulation alterations under ICIs and CAR T therapies are concerning, these results might be influenced by the retrospective study design and the heterogeneous patient populations. Importantly, numerous promising new T cell-based immunotherapies are currently under investigation for various cancers and are expected to become very prominent therapy options in the near future. Therefore, coagulopathies and thrombosis under T cell-directed immuno- and anti-cancer therapies is important. Our review provides an overview of the current understanding of ICI- and CAR T-associated thromboembolism. We discuss pathogenic mechanisms of inflammation-associated coagulation activation and explore potential biomarkers for VTE.

Keywords

immune checkpoint inhibitors - CAR T cells - hypercoagulability - thromboinflammation - cancer


Publikationsverlauf

Eingereicht: 05. August 2024

Angenommen: 27. Januar 2025

Artikel online veröffentlicht:
07. Mai 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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