The efficacy, safety, and impact of various clinical-pathological characteristics on the adjuvant immune checkpoint blockade in resected melanoma

The application of adjuvant immune checkpoint blockade (ICB) has been approved in melanoma since 2015. However, the efficacy and safety profiles of PD-1/PD-L1 blockade monotherapy have not been systematically evaluated. Moreover, the predictive value of routinely acquired clinicopathological and molecular characteristics for outcomes remains inconclusive. We searched the randomized controlled trials (RCTs) on adjuvant mono-immunotherapy in melanoma patients. Hazard ratios (HRs) were utilized to assess Recurrence-free survival (RFS) and distant metastasis-free survival (DMFS). Odds ratios (ORs) were applied to analyze treatment-related adverse event (TRAE), immune-related TRAE (IR-TRAE), serious TRAE, treatment discontinuation due to TRAE, and fatal adverse event (FAE). Totally, 2896 patients from 4 RCTs were included here; adjuvant mono-immunotherapy was associated with better RFS (HR, 0.60; 95% CI 0.53–0.68) and DMFS (HR, 0.62; 95% CI 0.54–0.71). No significant interactions were observed between treatment and age ( P interaction = 0.80), sex ( P interaction = 0.50), PD-L1 expression ( P interaction = 0.76), or BRAF mutation ( P interaction = 0.81). Compared with controls, adjuvant immunotherapy significantly increased the risk of any-grade TRAE (81.17% vs 62.39%; OR 2.81; 95% CI 1.86–4.26), high-grade TRAE (14.50% vs 3.84%; OR 4.58; 95% CI 3.33–6.31); any-grade IR-TRAE (21.76% vs 4.81%; OR 5.83; 95% CI 4.58–7.41), high-grade IR-TRAE (9.64% vs 1.15%; OR 9.38; 95% CI 5.09–17.28), serious TRAE (18.74% vs 2.23%; OR 5.04; 95% CI 2.73–9.30), treatment discontinuation due to TRAE (21.45% vs 6.24%; OR 6.98; 95% CI 4.33–11.27), and potential FAE (0.13% vs 0.00%; OR 1.59; 95% CI 0.29–8.82). Adjuvant immunotherapy is associated with favorable outcomes and, more importantly, greatly increases severe toxicities. Clinicians need to meticulously monitor patients to minimize the risk of treatment discontinuation in individuals with potentially curable melanoma. Future investigations should prioritize the identification of accurate biomarkers for adjuvant immunotherapy.