Patterns of toxicity burden for FDA-approved immune checkpoint inhibitors in the United States

Background Immune-related adverse events (irAEs) are a common phenomenon in cancer patients treated with immune checkpoint inhibitors (ICIs). Surprisingly, the toxicity burdens of these irAEs have not been illustrated clearly. In this study, we analyzed irAEs for seven FDA-approved ICIs in cancer treatment to show the pattern of toxicity burden among cancer patients.Methods irAEs associated with seven FDA-approved ICIs, including three PD-1 inhibitors (cemiplimab, nivolumab and pembrolizumab), three PD-L1 inhibitors (atezolizumab, avelumab and durvalumab), and one CTLA-4 inhibitor (ipilimumab), were analyzed based on data from 149,303 reported cases (from January 1, 2015 to June 30, 2022) collected from the FDA Adverse Events Reporting System (FAERS) public dashboard. Proportions of serious irAEs and correlations with tumor type, age and sex were assessed via R package and GraphPad software.Results irAEs related to anti-PD-1 ICIs required less hospital care resources compared with anti-PD-L1 and anti-CTLA-4 ICIs. Patients treated with pembrolizumab had relatively fewer serious cases. Treatment with ICIs led to the highest probability of serious irAEs in patients with lung cancer. Respiratory, thoracic and mediastinal disorders' and gastrointestinal disorders' were the two most common groups of disorders caused by the seven ICIs studied. Cardiac disorders' was the main type of disorders caused by these ICIs in cancer patients aged 65-85, while reproductive system and breast disease' was the main type of disorder in cancer patients aged 18-64. Respiratory, thoracic, mediastinal diseases' and reproductive system and breast diseases' were the main types of disorders associated with treatment with these ICIs in male and female patients, respectively.Conclusion Tissue and organ toxicities of ICIs are age and sex specific. There are risks of respiratory and urinary system toxicity in male patients and reproductive system toxicity in female patients treated with the ICIs studied. Future studies on the toxicity burden of ICIs should incorporate age and sex differences to better understand the relevance of ICI toxicity burden to human immune function to develop appropriate tumor immune and therapeutic interven-tion strategies.

Automated summary

This study analyzes immune-related adverse events (irAEs) associated with seven FDA-approved immune checkpoint inhibitors (ICIs) in cancer treatment, revealing the pattern of toxicity burden among patients. The findings highlight that irAEs related to anti-PD-1 ICIs require fewer hospital care resources compared to anti-PD-L1 and anti-CTLA-4 ICIs. Age and sex have specific impacts on tissue and organ toxicities of ICIs.