Thrombotic complications in patients treated with immune checkpoint inhibitors: a retrospective study of incidence, risk factors, and survival outcomes.
Awada A, Ghais A, et al. • Frontiers in immunology • 2026
Thrombotic events occurred in 16.6% of patients treated with immune checkpoint inhibitors and were independently associated with significantly worse overall survival (HR 2.55, 95% CI 1.89-3.43; p < 0.001).
Key Findings
Results
The overall incidence of thrombotic events in patients receiving immune checkpoint inhibitors was 16.6%.
750 adult patients treated with ICIs at a tertiary academic center were retrospectively reviewed.
125 thrombotic events occurred over a median follow-up of 25 months.
Of the 125 thrombotic events, 105 (84.0%) were venous thromboembolism (VTE) and 20 (16.0%) were arterial thromboembolism (ATE).
Thrombotic events were classified as VTE or ATE occurring from ICI initiation through follow-up.
Results
Thrombotic events in ICI-treated patients clustered early in the treatment course, with the majority occurring within the first two years.
38% of thrombotic events occurred within the first 6 months of ICI initiation.
56% occurred within 12 months.
67% occurred within 18 months.
74% occurred within 24 months of ICI initiation.
Results
Prior VTE, lower baseline hemoglobin, and older age at immunotherapy initiation were independent predictors of thrombotic events.
Prior VTE was associated with increased risk of thrombotic events (HR 1.84, 95% CI 1.12-3.01; p = 0.015).
Lower baseline hemoglobin was inversely associated with thrombotic event risk (HR 0.88 per unit increase, 95% CI 0.80-0.99; p = 0.036).
Older age at immunotherapy initiation was associated with increased risk (HR 1.07 per year increase, 95% CI 1.04-1.11; p < 0.001).
Predictors were identified using multivariable Cox proportional hazards models.
Results
Thrombotic events were independently associated with significantly worse overall survival in ICI-treated patients.
Thrombotic events were associated with significantly worse overall survival by log-rank test (p < 0.001).
In multivariable analysis, thrombotic events remained independently associated with mortality (HR 2.55, 95% CI 1.89-3.43; p < 0.001).
Kaplan-Meier methods were used to evaluate survival impact.
Results
Prior thrombotic events and a Khorana score ≥2 were independently associated with worse overall survival.
Prior thrombotic events were independently associated with worse OS (HR 1.86, 95% CI 1.29-2.69; p = 0.001).
A Khorana score ≥2 was independently associated with worse OS (HR 1.31, 95% CI 1.13-1.50; p < 0.001).
These associations were identified in multivariable Cox proportional hazards models.
The Khorana score is a validated risk assessment tool for cancer-associated thrombosis.
What This Means
This research suggests that blood clots — both in veins (venous thromboembolism) and arteries (arterial thromboembolism) — are a relatively common complication in cancer patients receiving immune checkpoint inhibitor (ICI) therapies, occurring in about 1 in 6 patients (16.6%) over a median follow-up period of about two years. The majority of these clotting events happened relatively early in treatment, with more than half occurring within the first year. The study identified three independent risk factors for developing a clot: having had a prior blood clot, being older at the time immunotherapy was started, and having a lower hemoglobin level (a measure of red blood cells) at the start of treatment.
This research also suggests that patients who develop thrombotic events while on ICIs face significantly worse survival outcomes — those who experienced a clot had more than twice the risk of death compared to those who did not, even after accounting for other factors. Additionally, patients with a history of prior clotting events or a Khorana score of 2 or higher (a standard clinical tool used to predict clot risk in cancer patients) also had worse overall survival, independent of whether they developed a new clot.
These findings matter because they highlight that clotting complications are not rare in ICI-treated cancer patients and can meaningfully worsen survival. This research suggests that identifying high-risk patients early — particularly those who are older, have a history of blood clots, or have low hemoglobin — could help clinicians implement closer monitoring or preventive strategies. The Khorana score may be a useful, readily available tool for stratifying risk in this population.
Awada A, Ghais A, Faraj S, Tarhini A, Rizkallah J, Mashmoushi N, et al.. (2026). Thrombotic complications in patients treated with immune checkpoint inhibitors: a retrospective study of incidence, risk factors, and survival outcomes.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1852772