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Background Immune checkpoint inhibitors (ICIs) have transformed the management of stage III melanoma, offering substantial improvements in survival outcomes. However, their use and continued treatment can be tempered by immune-related adverse events (irAEs). 1 Emerging evidence suggests a potential link between the development of irAEs and improved overall survival (OS) and recurrence-free survival (RFS).2 Despite this, the relationship between irAEs and patterns of disease recurrence—particularly the location of distant metastases—remains poorly characterized. To address this gap, we investigated distant metastasis-free survival (DMFS), RFS, and the anatomical distribution of distant metastases in patients with stage III melanoma treated with ICIs.Methods Retrospective chart review identified 171 patients with stage III melanoma treated with adjuvant ICI since 2017. Distant metastasis was considered any recurrence of disease that was not local cutaneous or in a locoregional lymph node/nodal basin. Distant metastasis-free survival was defined as the time from the start of immunotherapy to the first occurrence of distant metastasis or death and was censored at the last follow-up for those alive without distant metastasis.Survivor distributions for RFS and DMFS were estimated using the Kaplan-Meier method, and differences between groups were assessed using the Log-Rank test. The effects of immune-related adverse events on RFS and DMFS were evaluated using multivariable Cox proportional hazards models.Results The median age was 64 years (range 24-94), and 54.4% were male, 45.6% female. 51 patients (29.8%) had 1 distinct irAE, 21 patients (12.3) had 2, and 3 patients (1.8) had 3. 76% of all irAEs were grade I-II, and 24% were grade III-IV. 49 patients (28.7%) experienced recurrence of disease; of those, 21 were distant, 19 were regional, and 9 were local. There was not a statistically significant difference in the distribution of recurrence locations (distant, regional, local, or none) between patients with and without irAEs (Chi-square p = 0.2860, table 1). When local recurrence was categorized into cutaneous and scar/mucosal subtypes, there remained no significant difference in recurrence patterns based on irAE status (Fisher’s exact p = 0.3739). Additionally, patients who had an irAE did not have any significant difference in DMFS (figure 1).Conclusions In patients with stage III melanoma treated with adjuvant immune checkpoint inhibitors, the occurrence of an irAE did not affect the location of distant metastases or DMFS.References Wang DY, Salem JE, Cohen JV, Chandra S, Menzer C, Ye F, Zhao S, Das S, Beckermann KE, Ha L, et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol. 2018;4:1721–1728. doi: 10.1001/jamaoncol.2018.3923Watson A, Goutam S, Stukalin I, et al. Association of immune-related adverse events, hospitalization, and therapy resumption with survival among patients with metastatic melanoma receiving single-agent or combination immunotherapy. JAMA Network Open. 2021;5(12):e2245596. doi:10.1001/jamanetworkopen.2022.45596Abstract 1052 Table 1Distribution of first recurrence location by irAE status*p-value from Chi-Square testAbstract 1052 Figure 1Kaplan-Meier plot of DMFS by irAE. The probability of DMFS at 1-year was 87% (95% CI: 0.79, 0.93) for the patients without irAE vs. 88% (95% CI: 0.78, 0.94) for those with irAE. There was no significant difference in DMFS between the presence of irAE