Simple SummaryImmune checkpoint inhibitors (ICIs) can cause granulomatous and sarcoid-like lesions (GSLs) in several organs, and limited data existing that adequately inform the incidence and severity. This study examined GSL incidence in patients with high-risk melanoma treated with CTLA4 or PD1 blocking adjuvant therapy in two randomized clinical trials, the ECOG-ACRIN E1609 and SWOG S1404. The investigation identified 11 GSL cases among 2878 patients treated with ICIs or high-dose IFNα-2b. Grade III events were dominantly reported. Lung, mediastinal lymph nodes, skin, subcutaneous tissue, and eye were implicated in the reported GSLs. In addition, 62 literature reports were summarized. In conclusion, GSLs following anti-CTLA4 or anti-PD1 adjuvant treatment were uncommonly reported.AbstractBackground: Treatment with immune checkpoint inhibitors (ICIs) has been linked to granulomatous and sarcoid-like lesions (GSLs) affecting different organs. This study sought to evaluate GSL incidence in patients with high-risk melanoma treated with cytotoxic T-lymphocyte antigen 4 (CTLA4) or programmed cell death 1 (PD1) blockade adjuvant therapy in two clinical trials: ECOG-ACRIN E1609 and SWOG S1404. Descriptions and GSL severity ratings were recorded. Methods: Data were collected from ECOG-ACRIN E1609 and SWOG S1404. Descriptive statistics along with GSL severity grades were reported. Additionally, a literature review for such cases was summarized. Results: A total of 11 GSL cases were reported among 2878 patients treated with either ICI or with High-Dose Interferon Alfa-2b (HDI) in ECOG-ACRIN E1609 and SWOG S1404 trials. Cases were numerically more commonly reported with ipi10, followed by pembrolizumab, ipi3, and HDI, respectively. Most of the cases were grade III. Further, organs involved included lung, mediastinal lymph nodes, skin and subcutaneous tissue, and eye. Furthermore, a summary of 62 reports in the literature was described. Conclusions: GSLs following anti-CTLA4 and anti-PD1 antibody therapy in patients with melanoma were reported unusually. Reported cases ranged in grade from I to III and appeared manageable. Careful attention to these events and their reporting will be essential to better guide practice and management guidelines.