Monitoring Pseudoprogression Using Circulating Small Extracellular Vesicles Expressing PD-L1 in a Melanoma Patient Treated With Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICI) have revolutionized the treatment of metastatic malignancy. However, unique immune response patterns can occur, such as pseudoprogression, which corresponds to new lesion development or temporary tumour growth followed by regression. Misidentifying pseudoprogression may halt ICI therapy, due to the absence of biomarkers to distinguish progression from pseudoprogression. In 2020, our team proposed small extracellular vesicles expressing PD-L1 (sEV-PD-L1) as a predictor of melanoma treatment response. We report a case of pseudoprogression in a patient treated with nivolumab and ipilimumab for metastatic melanoma, and showing reduced circulating sEV-PD-L1. To our knowledge, this is the first report of PD-L1 monitoring in circulating sEV during pseudoprogression under ICI. A decrease in PD-L1 in circulating sEV might be an early sign of disease response to ICI, and may help to diagnose pseudoprogression. This case supports further evaluation of sEV-PD-L1 to identify responder patients to ICI, especially in case of pseudoprogression. Trial Registration: EXOMEL1 P/2018/40 1 AC-2015-2496/DC-2014-2086. NCT05744076.