CLOT+

BACKGROUND: Little is known about venous thromboembolism (VTE) and arterial thromboembolism (ATE) risk in melanoma patients receiving immune checkpoint inhibitors (ICIs) compared with other therapies.

OBJECTIVES: We assessed the incidence, risk factors, and impact of thromboembolism (TE) on survival in patients receiving ICIs, chemotherapy, or targeted therapy.

METHODS: We conducted a cohort study using the Surveillance, Epidemiology, and End Results-Medicare database to evaluate TE rates in patients treated with ICIs, chemotherapy, or BRAF/MEK inhibitors from 2008 to 2019, within 2 years after treatment initiation. Associations among TE, treatment, and clinical risk factors were evaluated using weighted competing risk regression. Overall survival was estimated by Kaplan-Meier and Cox regression models.

RESULTS: Among 6218 patients, 62.1% (n = 3860) received first-line ICIs, 30.4% (n = 1890) received chemotherapy, and 7.5% (n = 468) received targeted therapy. The cumulative incidence of VTE was similar across all treatment types: 7.7% for ICIs, 8.4% for chemotherapy, and 7.4% for targeted therapy at 12 months (P = .80). Similarly, ATE rates were 5.3% for ICIs, 5.0% for chemotherapy, and 6.5% for targeted therapy at 12 months (P = .30). A history of VTE (subdistribution hazard ratio [SHR], 2.81 [95% CI, 2.19-3.61]) and brain metastases (SHR, 1.33 [95% CI, 1.06-1.66]) were associated with an increased risk of VTE. Compared with chemotherapy, ICIs and targeted therapy had a similar VTE risk (P > .05). For ATE, cardiovascular disease (SHR, 1.49 [95% CI, 1.14-1.93]), diabetes mellitus (SHR, 1.27 [95% CI, 1.04-1.57]), a history of ATE (SHR, 1.61 [95% CI, 1.13-2.29]), and antiplatelet therapy (SHR, 1.37 [95% CI, 1.03-1.83]) were associated with increased risk. Patients with VTE or ATE experienced a 2-fold worse survival (hazard ratio [HR], 2.17 [95% CI, 1.64-2.87] and HR, 2.58 [95% CI, 1.92-3.47], respectively). In the ICI subanalysis, the ipilimumab/nivolumab combination had a higher cumulative incidence of VTE: 11.9% at 12 months, 9.3% for ipilimumab, 7.5% for pembrolizumab, and 5.8% for nivolumab (P < .05). Compared with nivolumab, the ipilimumab/nivolumab combination (SHR, 1.66 [95% CI, 1.09-2.54]) and ipilimumab (SHR, 1.43 [95% CI, 1.03-2.00]) had a higher VTE risk. VTE and ATE were associated with worse survival (HR, 3.24 [95% CI, 2.30-4.58] and HR, 1.89 [95% CI, 1.20-2.99], respectively).

CONCLUSION: ICIs, chemotherapy, and targeted therapy are associated with a high incidence of TE, and TE is associated with substantially worse survival.

No subscriber has commented on this article yet.