Survival after cessation of immunotherapies in melanoma: A systematic review and meta-analysis

Background: Immune-checkpoint inhibitor (ICI) therapy elicits durable responses in a subset of patients with advanced melanoma. However, the appropriate timing for treatment cessation remains an unresolved issue. Moreover, some patients are required to discontinue therapy due to the occurrence of severe adverse events. Upon treatment cessation, a subset of patients maintains a durable response, while some patients relapse and require rechallenge with ICI. Criteria for a safe stop of ICI have not been established. Objectives: The aim of this systematic review and meta-analysis was to evaluate the durability of response in melanoma patients who discontinued ICI therapy. Furthermore, the outcome of patients who electively stopped therapy was compared to that of patients who discontinued therapy due to adverse events. Methods: MEDLINE/PubMed, Embase and the Cochrane Library were searched for studies reporting outcomes after ICI discontinuation in patients with advanced melanoma. Pooled 1- to 3-year progression-free survival (PFS) and overall survival (OS) rates were estimated using random-effects models. The impact of the reason for treatment discontinuation, therapy regime and treatment duration on relapse-free survival was evaluated. Results: Twenty studies including 1832 patients were analysed. The pooled 1- and 3-year PFS rates after therapy stop were 86% (95% CI 80%–91%) and 71% (95% CI 64%–77%). A significantly higher 1-year PFS rate was observed in patients who electively discontinued treatment in contrast to toxicity-related therapy cessation (91% vs. 79%). Longer ICI treatment was associated with a higher PFS rate. 1- and 3-year OS rates post ICI treatment discontinuation were 96% (95% CI 91%–99%) and 86% (95% CI 79%–92%). Conclusions: Most patients remained relapse-free after ICI treatment. Patients with a treatment duration of at least 2 years are ideal candidates for treatment cessation, while treatment discontinuation may be considered after at least 1 year of ICI. PROSPERO number: CRD42024543781.