Document resource
Background Recent analyses offer conflicting evidence regarding the implications of an immune-related adverse event (irAE) on survival in patients with melanoma treated with immune checkpoint inhibitors (ICIs). For example, studies published between 2021 and 2022 indicate that an irAE observed during treatment with ICIs was associated with longer overall survival (OS). 1 2However, a 2024 review of 14 randomized controlled trials evaluating ICI use in patients with melanoma suggests there is no association between irAE and OS.3 We present melanoma-specific survival (MSS) and other survival metrics in patients with stage III melanoma treated with ICIs at a tertiary care center to provide clarification on this topic.Methods 171 patients with stage III melanoma diagnosed since 2017 were identified via retrospective chart review. MSS was defined as the time from starting immunotherapy to death due to melanoma. The cumulative incidence function was used to estimate the probability of MSS, and the Fine and Gray model was used to evaluate the effects of covariates (age, BMI, gender, pathologic stage). Gray’s test was used to compare cumulative incidence curves between groups. Survivor distributions for OS, progression/recurrence-free survival (PRFS), and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method, and the effects of irAEs were evaluated using multivariable Cox proportional hazards models.Results 43.86% of patients experienced an irAE and 30.39% of irAEs were grade III-IV ( table 1). The presence of an irAE was not significantly associated with MSS (cumulative incidence of 3.2% vs. 3.0% at 12 months in patients with or without irAE, respectively). This extended to OS, PRFS, and DMFS. The presence of multiple irAEs also did not affect survival. There was no association between irAE and MSS when selecting a particular irAE type (colitis vs. non-colitis, hepatitis vs. non-hepatitis, and pneumonitis vs. non-pneumonitis). MSS was significantly associated with irAE grade, with a cumulative incidence of 8.4% for patients with grade III-IV irAE vs 0% for patients with grade I-II irAE (figure 1, p=0.0342). This association was not present with OS, PRFS or DMFS. Stopping ICI treatment due to irAE did not have a significant difference in any survival outcome compared to not stopping treatment, regardless of whether treatment was eventually resumed.Conclusions The presence of an irAE was not associated with MSS, OS, PRFS or DMFS in patients with stage III melanoma treated with ICIs, although irAE grade was associated with MSS. Stopping or pausing treatment due to irAE did not affect survival.References Watson 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 Netw Open. 2021;5(12):e2245596.Ksienski D, Truong PT, Wai ES, et al. Survival outcomes following discontinuation of ipilimumab and nivolumab for advanced melanoma in a population-based cohort. Clin Oncol. 2022;33(12):e561-e569.Euvrar R, Robert M, Mainbourg S, et al. Association between immune-related adverse events in patients treated with immune checkpoint inhibitors in melanoma: a surrogacy analysis. Fundam Clin Pharmacol. 2024;38(2):369–379.Abstract 1054 Table 1Demographic and Clinical Characteristics (N=171)Abstract 1054 Figure 1Cumulative incidence of melanoma-specific death by irAE grade. At 12 months, cumulative incidence was 3.2% (95% CI: 0.84%–8.20%) for those without irAE, 0% (95% CI: 0.00–0.00%) for those with irAE grade I-II, and 8.4% (95% CI: 1.38–23.87%) for those with irAE grade III-IV. The difference was significant (p=0.0342)