Purpose: Immune checkpoint inhibitors (ICIs) improve recurrence outcomes in stage III melanoma but can cause immune-related adverse events (irAEs) of varying severity. While some studies suggest irAEs correlate with improved survival, findings remain inconsistent. Optimal management of recurrent stage III melanoma after adjuvant ICI therapy is also unclear. Here, we evaluate the impact of irAEs on survival and describe subsequent treatments in patients with recurrent stage III melanoma. Patients and Methods: We identified 171 patients with stage III melanoma treated with adjuvant ICIs since 2017. Clinical endpoints included overall survival, progression-free survival, distant metastasis-free survival, melanoma-specific survival, and time-to-irAE, which were analyzed using Kaplan–Meier method, Cox model, and Fine–Gray’s method. Cox model with time-varying covariate modeling addressed immortal-time bias. Subgroup analysis examined survival by irAE type, grade, and treatment resumption. Results: irAEs occurred in 43.86% of patients, with dermatitis (17.64%), colitis (16.67%), and hypothyroidism (15.69%) the most common. irAE presence did not impact survival outcomes. Thirty-one grade 3+ irAEs occurred, which were linked to increased short-term melanoma-specific mortality. Immune-related hepatitis was associated with higher mortality risk in multivariable modeling. Recurrence or progression occurred in 28.65% of patients, with 38.78% located at a distal site. Among those who started additional medical treatment, 42.86% received dual-checkpoint inhibitor therapy and 14.29% enrolled in clinical trials. Conclusion: Our findings do not support an association between irAEs and survival in patients with stage III melanoma. However, specific types of events, particularly hepatitis, may increase mortality. Prospective studies are needed to clarify optimal treatment after recurrence.

Background: Elderly patients have low utilization of adjuvant ICIs, although they achieve similar RFS benefits as younger patients. It remains unclear why elderly patients use adjuvant ICIs less frequently and whether toxicity impacts treatment utilization. Methods: Adult patients with stage III melanoma treated from 2017 to 2023 at a single academic cancer center were retrospectively identified. Multivariable logistic regressions evaluated the association of age with receipt of adjuvant ICIs and toxicity. RFS was assessed using Kaplan–Meier and multivariable Cox proportional hazards regression. Results: Among 240 patients, those aged ≥ 75 years were less likely to receive adjuvant ICI than those aged 18–74 years (aOR: 0.30; 95% CI: 0.11–0.80). Among 53 (22.1%) patients who did not receive adjuvant ICI, 58% declined treatment, 15% were not offered adjuvant ICI by provider, 9% had a comorbid autoimmunity, and 6% had another comorbidity. A total of 12% of patients aged 75–80 years old declined treatment versus 33% of those aged 80–90 years old. Older age was not associated with toxicity, treatment interruption, or discontinuation from adjuvant ICI. Adjuvant ICI was associated with low recurrence (aHR: 0.76; 95% CI: 0.63–0.92), whereas age ≥ 75 years was associated with higher recurrence risk (aHR: 1.79; 95% CI: 1.04–3.10) and low overall survival (aHR: 3.07; 95% CI: 1.43–6.57) compared to patients aged 18–74 years. Conclusions: Older patients with stage III melanoma were less likely to receive adjuvant ICIs, despite similar toxicity, treatment interruption, and discontinuation rates across age groups. Because adjuvant therapy is associated with lower recurrence risk, efforts to better understand and address age-related differences in treatment use are warranted.