Age-stratified outcomes of immune checkpoint inhibitors in geriatric patients with melanoma: A real-world cohort study.

Abstract

e13779 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of melanoma and are used across multiple disease stages. Geriatric patients comprise a rapidly growing proportion of patients with melanoma but remain underrepresented in clinical trials, limiting real-world age-stratified data on ICI outcomes in the geriatric population. Methods: We conducted a multicenter retrospective cohort study using the TriNetX platform to compare ICI outcomes in patients aged 65-74 years versus ≥75 years. Patients with Melanoma who had received pembrolizumab, nivolumab, atezolizumab, cemiplimab, durvalumab, and/or ipilimumab were included. We excluded patients receiving concurrent chemotherapy, those with carcinoid tumors, neuroendocrine tumors and hematologic/lymphoid malignancies. Patients with ulcerative colitis, microscopic colitis, Crohn’s disease and history of organ transplant were also excluded to minimize confounding due to chronic immunosuppressive therapy. The index date was first ICI administration. After 1:1 propensity score matching on demographic variables, cohort 1 (age 65-74 years) and cohort 2 (age ≥75 years) included 6223 patients each. The measure of association analysis was used to calculate the proportion of patients with outcomes and survival was analyzed using Kaplan-Meier analysis. The primary outcome was all-cause mortality. Secondary outcomes included ICU admission, systemic corticosteroid initiation, pneumonitis, gastrointestinal colitis/enterocolitis, hepatitis, myocarditis and the use of ICD-10 code for adverse effects of ICIs (T45.AX5 A/D/S). Results: All-cause mortality was significantly lower among patients with melanoma aged 65–74 compared with those aged ≥75 years receiving ICI (27.6% vs 39.1%). The risk difference was −11.4% (95% CI -0.131 to -0.098; p < 0.001), with an odds ratio of 0.596 (95% CI 0.553 to 0.643). No significant age-based differences were observed in ICU admission, myocarditis, or pneumonitis. However, incidence of hepatitis (20.9% vs 16.2% p < 0.001), gastrointestinal colitis/enterocolitis (13.9% vs 10.7% p < 0.001), systemic corticosteroid use (79.8% vs 74.3% p < 0.001) and use of ICD-10 code for adverse effects of ICIs (1.7% vs 1.1% p = 0.005) was more frequent among patients aged 65–74 years. Conclusions: Among patients with melanoma treated with ICIs, those aged ≥75 years had higher all-cause mortality, but had lower rates of ICI-related complications. In contrast, patients aged 64-75 years had lower all-cause mortality but higher incidences of hepatitis, colitis/enterocolitis and systemic steroid use. These findings highlight clinically meaningful differences within the geriatric population, potentially influenced by age-related immune dysregulation, immunosenescence, and co-morbidity burden, and underscore the need for more age-stratified research in geriatric oncology.