Immune checkpoint inhibitor-associated risk for venous thromboembolism: a comprehensive analysis

Background The relationship between venous thromboembolism (VTE) and immune checkpoint inhibitor therapy (ICI) is unclear. This analysis investigates the incidence of and risk factors for VTE in VTE-naive patients with cancer receiving ICI treatment.Methods A retrospective cohort study of patients r...

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Main Authors: Jean M Connors, F Stephen Hodi, Michael Manos, Anita Giobbie-Hurder, Tamara A Sussman, Nicole R LeBoeuf, Ian D Dryg, Jason L Weirather
Format: Article
Language:English
Published: BMJ Publishing Group 2025-05-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/13/5/e010761.full
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author Jean M Connors
F Stephen Hodi
Michael Manos
Anita Giobbie-Hurder
Tamara A Sussman
Nicole R LeBoeuf
Ian D Dryg
Jason L Weirather
author_facet Jean M Connors
F Stephen Hodi
Michael Manos
Anita Giobbie-Hurder
Tamara A Sussman
Nicole R LeBoeuf
Ian D Dryg
Jason L Weirather
author_sort Jean M Connors
collection DOAJ
description Background The relationship between venous thromboembolism (VTE) and immune checkpoint inhibitor therapy (ICI) is unclear. This analysis investigates the incidence of and risk factors for VTE in VTE-naive patients with cancer receiving ICI treatment.Methods A retrospective cohort study of patients receiving any type or combination of ICI from 2009 to 2022 at Dana-Farber Cancer Institute was conducted to identify VTE occurring after initiation of ICI treatment. Cumulative incidences of VTE were determined using Fine and Gray’s methods. Associations between VTE, ICI regimens, and clinical risk factors were evaluated using propensity-score stratified, multivariable Cox proportional hazards models.Results In 10,638 patients without a prior history of VTE, the 6-month cumulative incidence of VTE was 7.6% (95% CI: 7.1% to 8.1%) and 11.1% (95% CI: 10.5% to 11.8%) at 12 months. Clinical risk factors included: age 15–59 (HR 1.27; 95% CI: 1.12 to 1.43; p=0.002), obesity (HR: 1.41; 95% CI: 1.16 to 1.71), and history of anticoagulation prior to ICI start (HR: 1.43; 95% CI: 1.26 to 1.61). Compared with pembrolizumab, treatment with ipilimumab/nivolumab increased the risk of VTE (HR: 1.36; 95% CI: 1.02 to 1.82), while durvalumab conveyed lower risk (HR: 0.52; 95% CI: 0.31 to 0.87). Treatment with programmed cell death ligand 1 had significantly reduced risk of VTE (HR: 0.79; 95% CI: 0.63 to 0.99) compared with programmed cell death 1 monotherapy. Dual ICI blockade with cytotoxic T lymphocyte antigen 4/PD-1 significantly increased the risk of VTE (HR: 1.43; 95% CI 1.12 to 1.84). Initiation of anticoagulation after starting ICI for indications other than VTE reduced the risk by 40% (HR: 0.60, 95% CI: 0.48 to 0.73).Conclusions ICI treatment appears to be independently associated with a high incidence of VTE in patients with cancer warranting further investigation.
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spelling doaj-art-c9c5c985f7b941d185eca75ab3a8df232025-08-20T02:28:32ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-05-0113510.1136/jitc-2024-010761Immune checkpoint inhibitor-associated risk for venous thromboembolism: a comprehensive analysisJean M Connors0F Stephen Hodi1Michael Manos2Anita Giobbie-Hurder3Tamara A Sussman4Nicole R LeBoeuf5Ian D Dryg6Jason L Weirather77 Division of Hematology, Brigham and Women’s Hospital, Boston, Massachusetts, USA2 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA4 Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA3 Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts, USA1 Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA6 Department of Dermatology, Center for Cutaneous Oncology, Brigham and Women’s Hospital, Boston, Massachusetts, USA3 Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts, USA3 Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts, USABackground The relationship between venous thromboembolism (VTE) and immune checkpoint inhibitor therapy (ICI) is unclear. This analysis investigates the incidence of and risk factors for VTE in VTE-naive patients with cancer receiving ICI treatment.Methods A retrospective cohort study of patients receiving any type or combination of ICI from 2009 to 2022 at Dana-Farber Cancer Institute was conducted to identify VTE occurring after initiation of ICI treatment. Cumulative incidences of VTE were determined using Fine and Gray’s methods. Associations between VTE, ICI regimens, and clinical risk factors were evaluated using propensity-score stratified, multivariable Cox proportional hazards models.Results In 10,638 patients without a prior history of VTE, the 6-month cumulative incidence of VTE was 7.6% (95% CI: 7.1% to 8.1%) and 11.1% (95% CI: 10.5% to 11.8%) at 12 months. Clinical risk factors included: age 15–59 (HR 1.27; 95% CI: 1.12 to 1.43; p=0.002), obesity (HR: 1.41; 95% CI: 1.16 to 1.71), and history of anticoagulation prior to ICI start (HR: 1.43; 95% CI: 1.26 to 1.61). Compared with pembrolizumab, treatment with ipilimumab/nivolumab increased the risk of VTE (HR: 1.36; 95% CI: 1.02 to 1.82), while durvalumab conveyed lower risk (HR: 0.52; 95% CI: 0.31 to 0.87). Treatment with programmed cell death ligand 1 had significantly reduced risk of VTE (HR: 0.79; 95% CI: 0.63 to 0.99) compared with programmed cell death 1 monotherapy. Dual ICI blockade with cytotoxic T lymphocyte antigen 4/PD-1 significantly increased the risk of VTE (HR: 1.43; 95% CI 1.12 to 1.84). Initiation of anticoagulation after starting ICI for indications other than VTE reduced the risk by 40% (HR: 0.60, 95% CI: 0.48 to 0.73).Conclusions ICI treatment appears to be independently associated with a high incidence of VTE in patients with cancer warranting further investigation.https://jitc.bmj.com/content/13/5/e010761.full
spellingShingle Jean M Connors
F Stephen Hodi
Michael Manos
Anita Giobbie-Hurder
Tamara A Sussman
Nicole R LeBoeuf
Ian D Dryg
Jason L Weirather
Immune checkpoint inhibitor-associated risk for venous thromboembolism: a comprehensive analysis
Journal for ImmunoTherapy of Cancer
title Immune checkpoint inhibitor-associated risk for venous thromboembolism: a comprehensive analysis
title_full Immune checkpoint inhibitor-associated risk for venous thromboembolism: a comprehensive analysis
title_fullStr Immune checkpoint inhibitor-associated risk for venous thromboembolism: a comprehensive analysis
title_full_unstemmed Immune checkpoint inhibitor-associated risk for venous thromboembolism: a comprehensive analysis
title_short Immune checkpoint inhibitor-associated risk for venous thromboembolism: a comprehensive analysis
title_sort immune checkpoint inhibitor associated risk for venous thromboembolism a comprehensive analysis
url https://jitc.bmj.com/content/13/5/e010761.full
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