Impact of immune-related adverse events on quality of life and physical functioning in older patients with solid tumors treated with immune checkpoint inhibitors

Abstract

Background: Immune checkpoint inhibitors (ICIs) improved survival in solid tumors but can cause immune-related adverse events (irAEs) that may affect quality of life (QOL) and physical functioning. The impact of severe irAEs on these outcomes remains unclear, particularly in frail older patients. This study evaluated the association between grade ≥ 3 irAEs and QOL and/or physical functioning over time in frail versus non-frail older patients receiving ICI therapy. Methods: Patients aged ≥ 65 years with solid tumors treated with ICIs (September 2018-February 2024), were prospectively included in this multicenter study. QOL and physical functioning were evaluated at baseline, 6, and 12 months. Multivariable logistic regression models, adjusted for confounders, evaluated associations between severe irAEs and an unfavorable outcome (decline in QOL and/or physical functioning, or mortality). Secondary outcomes included the association of frailty and unfavorable outcomes, hospitalizations related to severe irAEs and treatment discontinuation due to irAEs. Results: Among 169 patients (median age: 73 years, IQR: 71–78), 58 % were frail. Severe irAEs occurred in 22 % of patients at 6 months and 27 % at 12 months, with no differences by frailty status. Unfavorable outcomes occurred in 45.6 % at 6 months and 56.2 % at 12 months, with frail patients at higher risk at 6 months (OR: 2.14, 95 %C.I.: 1.01–4.52). Severe irAEs were not significantly associated with unfavorable outcomes at 6 or 12 months in the overall cohort or when stratified by frailty. Hospitalization rates were higher in frail patients (44 % vs. 19 %; p = 0.016), but not due to severe irAEs. Conclusion: Severe irAEs were not associated with unfavorable immunotherapy outcomes, regardless of frailty status. However, frailty was associated with unfavorable outcomes.