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Demographic Factors Associated with Toxicity in Patients Treated with Anti-Programmed Cell Death-1 Therapy
Kaustav P Shah1, Haocan Song2, Fei Ye2
1Vanderbilt University School of Medicine, Nashville, Tennessee.
Abstract:
Immune checkpoint inhibitors (ICI) are now routinely used in multiple cancers but may induce autoimmune-like side effects known as immune-related adverse events (irAE). Although classical autoimmune diseases have well-known risk factors, including age, gender, and seasonality, the clinical factors that lead to irAEs are not well-defined. To explore these questions, we assessed 455 patients with advanced melanoma treated with ICI at our center and a large pharmacovigilance database (VigiBase). We found that younger age was associated with a similar rate of any irAEs but more frequent severe irAEs and more hospitalizations (OR, 0.97 per year). Paradoxically, however, older patients had more deaths and increased length of stay (LOS) when hospitalized. This was partially due to a distinct toxicity profile: Colitis and hepatitis were more common in younger patients, whereas myocarditis and pneumonitis had an older age distribution both in our center and in VigiBase. This pattern was particularly apparent with combination checkpoint blockade with ipilimumab and nivolumab. We did not find a link between gender or seasonality on development of irAEs in univariate or multivariate analyses, although winter hospitalizations were associated with marginally increased LOS. This study identifies age-specific associations of irAEs.
Insights
Younger patients on immune checkpoint inhibitors (ICI) face more severe immune-related adverse events (irAEs), while older patients experience higher mortality. Age significantly impacts ICI toxicity profiles, influencing specific irAEs like colitis versus myocarditis.
Area of Science:
- Oncology
- Immunology
- Pharmacovigilance
Background:
- Immune checkpoint inhibitors (ICI) are crucial cancer therapies.
- Immune-related adverse events (irAEs) are common side effects.
- Risk factors for irAEs are not fully understood, unlike classical autoimmune diseases.
Purpose of the Study:
- To investigate clinical factors, particularly age, influencing irAE development and outcomes.
- To compare irAE patterns in advanced melanoma patients treated with ICI.
Main Methods:
- Retrospective analysis of 455 advanced melanoma patients treated with ICI.
- Utilized a large pharmacovigilance database (VigiBase) for comparison.
- Assessed associations between age, gender, seasonality, and irAEs.
Main Results:
- Younger age correlated with more severe irAEs and hospitalizations.
- Older patients had increased mortality and longer hospital stays.
- Distinct age-related irAE profiles observed: colitis/hepatitis in younger, myocarditis/pneumonitis in older patients.
- Combination ICI therapy (ipilimumab/nivolumab) showed pronounced age-specific patterns.
- No significant link found between gender or seasonality and irAE development.
Conclusions:
- Age is a critical factor in irAE development and outcomes.
- Age-specific toxicity profiles necessitate tailored monitoring and management strategies for patients on ICI.
- Further research into age-related mechanisms of irAEs is warranted.
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