J Thromb Haemost. 2026 Sep 12:S1538-7836(26)00565-9. doi: 10.1016/j.jtha.2026.09.005. Online ahead of print.
ABSTRACT
BACKGROUND: Little is known about venous thromboembolism (VTE) and arterial thromboembolism (ATE) risk in melanoma patients receiving immune checkpoint inhibitors (ICI), compared to other therapies.
OBJECTIVES: We assessed incidence, risk factors, and impact on survival of thromboembolism (TE) in patients receiving ICI, chemotherapy, or targeted therapy.
METHODS: We conducted a cohort study using SEER-Medicare to evaluate TE rates in patients treated 2008-2019 with ICI, chemotherapy, or BRAF/MEK inhibitors within two years after treatment initiation. Associations between TE, treatment, and clinical risk factors were evaluated using weighted competing risk regression (CRR). Overall survival was estimated by Kaplan-Meier and Cox regression models.
RESULTS: Among 6,218 patients, 62.1% (3,860) received first line ICI, 30.4% (1,890) chemotherapy, and 7.5% (468) targeted therapy. Cumulative incidence of VTE was similar among all treatment types: 7.7% for ICI, 8.4% for chemo, and 7.4% for targeted therapy at 12 months (p=0.80). Similarly, ATE rates were 5.3% for ICI, 5.0% for chemo, and 6.5% for targeted therapy at 12 months (p=0.30). History of VTE (SHR: 2.81; [95%CI: 2.19-3.61]) and brain metastases (SHR: 1.33 [1.06-1.66]) were associated with increased risk of VTE. When compared to chemotherapy, ICI and targeted therapy had similar VTE risk (p>0.05). For ATE, cardiovascular disease (SHR: 1.49 [1.14-1.93]), diabetes mellitus (SHR: 1.27 [1.04-1.57]), history of ATE (SHR: 1.61 [1.13-2.29]), and antiplatelet therapy (SHR: 1.37 [1.03-1.83]) were associated with increased risk. Patients with VTE or ATE experienced two-fold worse survival (HR: 2.17 [1.64-2.87] and HR: 2.58 [1.92-3.47], respectively). In ICI sub-analysis, combination ipilimumab/nivolumab had higher cumulative incidence of VTE: 11.9% at 12 months, 9.3% for ipilimumab, 7.5% for pembrolizumab, and 5.8% for nivolumab (p<0.05). When compared to nivolumab, combination ipilimumab/nivolumab (SHR: 1.66 [1.09-2.54]) and ipilimumab (SHR: 1.43 [1.03-2.00]) had greater VTE risk. VTE and ATE were associated with worse survival (HR: 3.24 [2.30-4.58] and HR: 1.89 [1.20-2.99], respectively).
CONCLUSIONS: ICI, chemotherapy, and targeted therapy are associated with a high incidence of TE; TE is associated with substantial worsening of survival.
PMID:42731732 | DOI:10.1016/j.jtha.2026.09.005