Thromboembolic events associated with immune checkpoint inhibitors: A real-world study of data from the food and drug administration adverse event reporting system (FAERS) database

Abstract

Background: Although there have been a few studies reporting thromboembolic events (TEEs) in patients treated with immune checkpoint inhibitors (ICIs), the detailed profile of the TEEs and the prothrombotic effects of ICIs remain mostly unknown.

Methods: Data from January 2004 to December 2019 in the FAERS database were retrieved. We investigated the clinical characteristics of the TEEs and conducted disproportionality analysis by using reporting odds ratios (ROR) to compare ICIs with the full database and other anti-cancer agents.

Results: We identified 1855 reports of TEEs associated with ICIs. Affected patients tended to be male (59.68%) and older than 65 (47.12%). The case-fatality rate of the reported TEEs was high (38%). The median time to onset (TTO) of all cases was 42 (interquartile range [IQR] 15-96) days and the median TTO of fatal cases (31 [IQR 13-73] days) was significantly shorter than non-fatal cases (50 [IQR 20-108] days, p = 0.000002). ICIs showed increased risks of VTE (ROR 2.81, 95% CI 2.69-2.95) and ATE (ROR 1.44, 95% CI 1.37-1.52) compared with the full database. Compared with protein kinase inhibitors, ICIs showed an increased risk of VTE (ROR 1.23, 95% CI 1.17-1.29), but only anti-PD-L1 showed an increased risk of cerebral ATE (ROR 1.38, 95% CI 1.08-1.76). Compared with chemotherapy, ICIs showed an increased risk of PE (ROR 1.14, 95% CI 1.07-1.21).

Conclusions: Our study suggested ICIs tend to increase risks of VTE and ATE. The poor clinical outcome and early onset of these events should attract clinical attention.

Keywords: CTLA-4; FAERS; Immune checkpoint inhibitor; PD-1; PD-L1; Thromboembolic event.