Immune checkpoint inhibitors for cancer and venous thromboembolic events

Jingyi Gong; Zsofia D Drobni; Raza M Alvi; Sean P Murphy; Ryan J Sullivan; Sarah E Hartmann; Hannah K Gilman; Hang Lee; Leyre Zubiri; Vineet K Raghu; Rebecca S Karp-Leaf; Amna Zafar; Daniel A Zlotoff; Matthew J Frigault; Kerry L Reynolds; Tomas G Neilan

doi:10.1016/j.ejca.2021.09.010

Immune checkpoint inhibitors for cancer and venous thromboembolic events

Eur J Cancer. 2021 Oct 15:158:99-110. doi: 10.1016/j.ejca.2021.09.010. Online ahead of print.

Authors

Affiliations

¹ Cardiovascular Imaging Research Center, Department of Radiology and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
² Cardiovascular Imaging Research Center, Department of Radiology and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
³ Cardiovascular Imaging Research Center, Department of Radiology and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Division of Oncology and Hematology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Massachusetts General Hospital Biostatistics Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Cardiovascular Imaging Research Center, Department of Radiology and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Cardio-Oncology Program, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: tneilan@mgh.harvard.edu.

Abstract

Background: Immune checkpoint inhibitors (ICIs) are widely used cancer treatments. There are limited data on the risk for developing venous thromboembolism (VTE) among patients on an ICI.

Methods: This was a retrospective study of 2854 patients who received ICIs at a single academic centre. VTE events, defined as a composite of deep vein thrombosis or pulmonary embolism, were identified by individual chart review and blindly adjudicated using standard imaging criteria. A self-controlled risk-interval design was applied with an 'at-risk period' defined as the two-year period after and the 'control period', defined as the two-year before treatment. The hazard ratio (HR) was calculated using a fixed-effect proportional hazards model.

Results: Of the 2854 patients, 1640 (57.5%) were men; the mean age was 64 ± 13 years. The risk for VTE was 7.4% at 6 months and 13.8% at 1 year after starting an ICI. The rate of VTE was > 4-fold higher after starting an ICI (HR 4.98, 95% CI 3.65-8.59, p < 0.001). There was a 5.7-fold higher risk for deep vein thrombosis (HR 5.70, 95% CI 3.79-8.59, p < 0.001) and a 4.75-fold higher risk for pulmonary embolism (HR 4.75, 95% CI 3.20-7.10, p < 0.001). Comparing patients with and without a VTE event, a history of melanoma and older age predicted lower risk of VTE, while a higher Khorana risk score, history of hypertension and history of VTE predicted higher risk.

Conclusions: The rate of VTE among patients on an ICI is high and increases after starting an ICI.

Keywords: Anticoagulation; Cancer; Cardio-oncology; Immune checkpoint inhibitors; Vascular medicine; Venous thromboembolism.

Abstract

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