Presentation Details
| Comparative Analysis of Bleeding and Thrombotic Risks Among Immune Checkpoint Inhibitors: Insights from the FDA Adverse Event Reporting System Emily L Paton1, Emma P Deloughery1, 2. 1Oregon Health & Science University, Department of Medicine, Portland, OR, USA.2Oregon Health & Science University, Department of Medicine, Division of Hematology & Medical Oncology, Portland, OR, USA |
Abstract
Background: Immune checkpoint inhibitors (ICIs) have become a cornerstone of treatment in various cancers. With the diverse risk profiles of ICIs, ongoing post-marketing surveillance is crucial to understand their safety profiles. Notably, concerns surrounding an elevated risk of both bleeding and thrombotic complications have emerged in the literature, though with some conflicting evidence. The FDA Adverse Event Reporting System (FAERS) aggregates reports from clinicians and patients detailing side effects presumed to be linked to specific pharmaceutical interventions. There is a lack of comparative analyses on bleeding and thrombotic risks across different ICIs among FAERS reports. Objectives: This analysis compares reported bleeding and thrombotic complications of approved ICIs by clinicians in FAERS. Methods: Using the FAERS database, adverse event data were gathered for approved ICIs: avelumab, atezolizumab, cemiplimab, durvalumab, ipilimumab, nivolumab, and pembrolizumab. Data were filtered by events of interest, including anemia, bleeding, hemolysis, venous thromboembolism (VTE)/pulmonary embolism (PE), and thrombocytopenia. The proportional reporting ratio (PRR) with a 95% confidence interval was used to compare rates of bleeding and thrombotic complications among ICIs. A PRR value greater than 2 was considered statistically significant. If a drug had fewer than 3 adverse events within a specific category, that drug was excluded from the analysis. Results: 76,036 total adverse events were reported for ICIs from 2006-2023. The PRR was used to compare rates of VTE/PE, anemia, bleeding, hemolysis, and thrombocytopenia. Of the ICIs, avelumab had the highest PRR for VTE/PE (1.17 atezolizumab vs 1.60 avelumab vs 1.01 cemiplimab vs 1.13 ipilimumab vs 0.89 nivolumab vs 1.02 pembrolizumab), thrombocytopenia (1.23 atezolizumab vs 1.80 avelumab vs 0.73 cemiplimab vs 0.93 ipilimumab vs 1.14 nivolumab vs 0.74 pembrolizumab), and bleeding (1.24 atezolizumab vs 1.38 avelumab vs 1.20 cemiplimab vs 1.13 ipilimumab vs 1.26 nivolumab vs 0.68 pembrolizumab), though this was not statistically significant. Atezolizumab had the highest PRR for anemia (1.79 atezolizumab vs 1.05 avelumab vs 1.43 cemiplimab vs 0.93 ipilimumab vs 1.14 nivolumab vs 0.73 pembrolizumab). Between ipilimumab, nivolumab, and pembrolizumab, nivolumab had the highest PRR for hemolysis (0.63 pembrolizumab vs 1.41 nivolumab vs 1.10 pembrolizumab; atezolizumab, avelumab, cemiplimab, and durvalumab were excluded due to fewer than 3 reported cases of hemolysis). Conclusions: Our results highlight that avelumab may have an increased risk of VTE/PE, thrombocytopenia, and bleeding compared to other approved ICIs, though statistical significance is not reached. Atezolizumab emerges with the highest PRR for anemia, also without statistical significance. Among pembrolizumab, nivolumab, and ipilimumab, nivolumab has the highest PRR of hemolysis. Our results may help guide future prospective studies or suggest to clinicians ICIs to avoid in patients with elevated bleeding or thrombotic risk.
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