Thromboembolic events associated with immune checkpoint inhibitors in cancer patients: A Bayesian network meta-analysis

Background: Immune checkpoint inhibitors (ICIs), which offer previously unknown therapeutic advantages, have revolutionized cancer treatment. However, the risk of thromboembolic events (TEEs) associated with ICIs remains unclear. The aim of this network meta-analysis (NMA) was to evaluate the incidence of TEEs in cancer patients receiving different treatment regimens. Methods: We searched for randomized clinical trials (RCTs) between January 2021 and December 2023 without restricting the cancer type. The percentages of TEEs were systematically extracted. An NMA was performed comparing atezolizumab, cemiplimab, durvalumab, ipilimumab, nivolumab, pembrolizumab, conventional therapy (which consists mainly of chemotherapy, targeted therapy, placebo, and their combinations), two ICI drugs, one ICI drug combined with conventional therapy, and two ICI drugs combined with conventional therapy. Additionally, subgroup analysis was conducted based on cancer type. Results: Eighty-three RCTs involving 54,736 patients were included. Patients receiving ICIs demonstrated comparable risks of arterial thromboembolism (ATE), deep vein thrombosis (DVT), myocardial infarction (MI), and cerebrovascular accidents (CVAs). Nivolumab (OR 0.39, 95 % CI 0.19 to 0.80) and two ICI drugs (OR 0.52, 95 % CI 0.29 to 0.89) had the lowest risk of venous thromboembolism (VTE) compared to two ICI drugs with conventional therapy. The risk of pulmonary embolism (PE) was greater for ipilimumab (OR 4.09, 95 % CI 1.13 to 15.51) than for nivolumab. For melanoma in the subgroup analysis, nivolumab significantly reduced the risk of VTE (OR 0.07, 95 % CI 0.00 to 0.76) compared to two ICI drugs. Among the single-ICI regimens, durvalumab was associated with the highest incidence of ATE, MI, and CVAs; ipilimumab had the highest incidence of VTE and PE; and pembrolizumab had the highest incidence of DVT. The combination of one ICI drug with conventional therapy was associated with a significantly greater risk of TEEs (except for MI) than the combination of two ICI drugs. Conclusions: Various ICI regimens in cancer patients exhibit clinically significant differences in the risks of TEEs. Nivolumab exhibited a favorable safety profile regarding VTE, while ipilimumab had the highest risk of both VTE and PE. Different ICI regimens require tailored risk management strategies to reduce TEEs.