Older Age Is Associated with Immune-Related AEs in Treatment with Immune Checkpoint Inhibitors

Older cancer patients (over 65) receiving immune checkpoint inhibitors (ICIs) are at a significantly increased risk of immune-related adverse events (irAEs) than younger patients, according to a study. These findings were published in the European Journal of Hematology.

“With the increased use of ICIs, it is essential to improve our understanding of irAEs,” wrote the study authors. “To date, most studies describing irAEs have been performed in clinical trial populations, which may not be an accurate description of irAEs in real-world populations. Also, identification of patients at increased risk of irAEs is needed as early recognition may improve irAE outcomes.”

The researchers retrospectively analyzed patients who received an ICI at a single center between January 2014 through October 2018. Minimum follow-up was 12 months. Kaplan-Meier curves were created for time to irAE development and resolution, and a Cox proportional hazards model was used to evaluate irAE risk associated with the following variables: age ≥65 years, female sex, non-Caucasian race, radiation in previous 6 months, current smoking status, melanoma, and combination ICI use (ipilimumab and nivolumab).

The total cohort included 131 patients. The overall rate of irAEs was 43.5%, occurring in 57 patients. Median time to irAE onset was 250 days (95% confidence interval (CI), 132-Not estimable). Dermatitis, thyroid dysfunction, and pneumonitis were the most common events.

“We detected a high rate of irAE and that irAE and subsequent management can be clinically burdensome in this patient population,” noted the study authors.

Of patients who developed an irAE, nearly two-thirds discontinued ICI therapy and nearly 60% initiated treatment with immunosuppressants. The factors most significantly associated with irAE development were: being aged ≥65 years (hazard ratio [HR]=1.80, 95% CI, 1.03-3.14) and being a current smoker (HR=2.26, 95% CI, 1.06-4.82).

The authors wrote in conclusion, “While further studies are needed to validate these findings, this study provides insights into the magnitude, time course, management of, and possible predictors of irAE in a real-world setting.”