Impact of geriatric impairments on outcomes of single-agent immunotherapy in solid tumors

Cancer is increasingly prevalent among older adults with geriatric impairments, yet the impact of frailty on immune checkpoint inhibitor (ICI) therapy outcomes remains underexplored. This study aims to assess the association between frailty and grade ≥3 immune-related adverse events (irAEs), clinical benefit, all-cause hospitalization, and mortality in older patients undergoing ICI therapy. Patients aged ≥65 years, treated with anti-PD-1 monotherapy for a solid malignancy (September 2018-February 2024), were prospectively included in this multicenter study. The association between frailty, components of the geriatric assessment, and number of impaired geriatric domains with the occurrence of grade ≥3 irAEs, all-cause hospitalization, and clinical benefit was analyzed using univariable and multivariable logistic regression. Cox proportional hazards models were used to analyze all-cause mortality. Among the 110 patients, 55% were classified as frail. Grade ≥3 irAEs occurred in 17.3%, with no significant difference between frail and non-frail patients (18.0% vs. 16.4%, p = .814). Frailty was associated with higher hospitalization (OR: 3.98, 95%C.I.: 1.20-13.19) and mortality risk (HR: 5.23, 95%C.I.: 1.81-15.11). Multimorbidity (Charlson comorbidity index score ≥3) was also associated with hospitalization (OR: 5.54, 95%C.I.: 1.81-16.99). Frailty and the number of impaired geriatric domains were not associated with clinical benefit of ICIs in the palliative treatment setting (p = .374, and p = .155, respectively). Frailty should not be considered a contraindication for ICI therapy, as this therapy is generally well-tolerated, even among older frail patients. Instead, frailty should be viewed as a relevant clinical factor for optimizing therapeutic decision-making and tailoring supportive interventions in older patients.