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Thromb Haemost 2023; 123(11): 1049-1056
DOI: 10.1055/s-0043-1769609
Stroke, Systemic or Venous Thromboembolism

Risk Factors of Venous Thromboembolic Disease in Cancer Patients Treated with Immune Checkpoint Inhibitor

Julien Denis le Sève
1   Nantes Université, CHU Nantes, Department of Internal and Vascular Medicine, Nantes, France
,
Alexis F. Guédon
1   Nantes Université, CHU Nantes, Department of Internal and Vascular Medicine, Nantes, France
,
Stéphanie Bordenave
2   Nantes Université, CHU Nantes, Department of Thoracic Oncology, Nantes, France
,
Christian Agard
1   Nantes Université, CHU Nantes, Department of Internal and Vascular Medicine, Nantes, France
,
Jérôme Connault
1   Nantes Université, CHU Nantes, Department of Internal and Vascular Medicine, Nantes, France
,
Marc-Antoine Pistorius
1   Nantes Université, CHU Nantes, Department of Internal and Vascular Medicine, Nantes, France
,
Gaelle Quéreux
3   Nantes Université, CHU Nantes, Department of Dermatology, Nantes, France
,
Olivier Espitia 
1   Nantes Université, CHU Nantes, Department of Internal and Vascular Medicine, Nantes, France
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Abstract

Background Immune checkpoint inhibitors (ICIs) have revolutionized the management of cancers. The risk factors and pathophysiological mechanisms of venous thromboembolic events (VTEs) of this new therapeutic class are still to be specified.

Methods The included patients had to have cancer and should be treated with ICI. Data analyzed included demographic data, biological data, and immune-related adverse events (IRAEs). We studied the prevalence of VTEs and the factors associated with VTEs.

Results Of 374 patients on ICI, over a median follow-up period of 15.2 months, the number of VTE was 50 (13.4%). The majority of patients were treated for metastatic melanoma or nonsmall cell lung cancer. There was no difference in prevalence or survival between cancer types. Patients with combined therapy composed of nivolumab and ipilimumab had higher 1-year cumulative VTE occurrence (29.3% [95% confidence interval [CI]: 9.7; 44.6]) than patients with pembrolizumab (14.9%, [95%CI: 2.5; 25.8], p = 0.03) or nivolumab (9.1%, [95% CI: 5.0; 12.9], p < 0.01). The presence of IRAE was associated with a higher risk of VTE occurrence compared with patients without any IRAE (1-year VTE cumulative incidence: 17.42% [95% CI: 9.5; 24.65] vs. 9.46% [95% CI: 5.18; 13.55], p = 0.04). There was a higher risk of VTE in patients treated with the combination of nivolumab and ipilimumab (adjusted subdistribution hazard ratio [SHR]: 3.71 [95% CI: 1.74; 7.90], p < 0.001) and in patients with IRAE (adjusted SHR: 2.14 [95% CI: 1.22; 3.75], p < 0.01).

Conclusion The prevalence of VTE was 14.2% under ICIs. IRAE and combine treatment of nivolumab and ipilimumab were associated with VTE. The pathophysiological mechanisms are multiple and complex with a possible link to aberrant activation of the immune system.

Keywords

cancer - pulmonary embolism - vein thrombosis - immune check point inhibitor - immune-related adverse event

Ethical Approval Statement

This study has received ethics board approval by GNEDS (Groupe Nantais d'Ethique dans le Domaine de la Santé), the local ethics committee of the University Hospital of Nantes.


Supplementary Material



Publication History

Received: 08 March 2023

Accepted: 25 April 2023

Article published online:
31 May 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

Comment to this article:

Immune Checkpoint Inhibitors and Venous Thromboembolism: The More Things Change…Thromb Haemost 2023; 123(11): 1057-1059
DOI: 10.1055/a-2121-9679

 

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