Treatment patterns in geriatric patients with melanoma and the effect of age on the efficacy of immunotherapy: Analysis from the real-world multicenter registry ADOREG

• Geriatric patients are underrepresented in clinical trials and data about optimized management are scant. • The interplay between immunosenescence, comorbidities and polypharmacy renders management challenging. • Older patients were treated mainly with anti-PD1 monotherapy, without an efficacy impairment. • High comorbidities burden did not compromise efficacy when anti-PD1 monotherapy was selected. • Assessment of biological age and impairment by comorbidities seems important for individualized approaches. Geriatric patients are underrepresented in clinical trials and data about optimized management are scant. The interplay between immunosenescence, comorbidities and polypharmacy renders management challenging. Older patients were treated mainly with anti-PD1 monotherapy, without an efficacy impairment. High comorbidities burden did not compromise efficacy when anti-PD1 monotherapy was selected. Assessment of biological age and impairment by comorbidities seems important for individualized approaches. Data on treatment approaches in geriatric melanoma patients are scant. Efficacy of oncologic treatments across age groups, with special focus on immunotherapy, and the impact of comorbidities were analyzed. A retrospective multicenter cohort study of the ADOREG registry included patients with cutaneous melanoma, who received oncological drugs at German skin cancer centers between 2013 and 2023. Outcomes were objective response rate (ORR), progression-free survival (PFS), melanoma-specific survival (MSS), toxicities and reasons for treatment discontinuation. Age groups were prespecified as <75 vs ≥75 years (geriatric), comorbidities were summarized by Charlson-Comorbidity-Index (CCI). Comparisons across groups were conducted with X 2 -test, survival outcomes were compared via log-rank tests. Of 14,356 melanoma patients, 8,213 met the inclusion criteria, 6,063 and 2,150 were <75 and ≥75 years old, respectively. Among the 3,646 patients with metastatic disease, older patients received fewer treatment lines and were less likely to undergo surgery, radiotherapy and systemic therapy. However, efficacy of any first-line treatment did not differ between both age groups (p=0.306). Immunotherapy selection at any line was similar in both groups (p=0.109), but geriatrics were treated mainly with first-line anti-PD1 monotherapy, whereas combination ICIs was preferred in younger patients. Efficacy was not impaired (PFS and MSS: p>0.05), while toxicity rates were lower. This pattern persisted across CCI categories. Age influenced treatment selection in melanoma patients. However, in geriatric patients, efficacy was not impaired, and a balanced toxicity profile was noticed, particularly for immunotherapy. Future studies considering biological age and impairment by comorbidities seems important to assess individualized treatment approaches.