Gene signature to predict hypophysitis in patients with melanoma treated with anti-PD-1 in adjuvant setting.

Abstract

e21562 Background: Adjuvant anti-PD-1 treatment has shown to improve recurrence free survival and distant metastases free survival in melanoma patients from stage II to IV. Until now ,we have no data about overall survival of these patients nor biomarkers to select them to the best therapy , avoiding in this way severe and some times durable toxicities.Hypophysitis is a rare immune-related adverse event (irAE) and in adjuvant setting may represent a chronic irAE that may affect quality of life , such as fertility in young people.There are no clinical factors able to predict hypophysitis due to adjuvant anti-PD-1 therapy. Methods: Gene profiling analysis was performed using NanoString IO360 panel from basal PBMCs of patients treated with anti-PD1 in adjuvant setting. Patient’s characteristics are reported in table1. ROC curves were used to determine the best cut off. Survival rates were evaluated and compared using the Kaplan–Meier method. Results: Eighty pts treated with adjuvant anti-PD-1were included in a retrospective analysis from December 2019 to September 2021. Among which 12 pts developed hyphosytis. Ten pts completed treatment regularly, while two were discontinued both at week 12 due to metastatic disease. A pts developed liver metastases, the other one liver, multiple lymph nodes and soft tissues metastases. Grade 2 hypophysitis was diagnosed as the only irAE in all pts (100%). Median time of onset was 3 months (9 pts ≤6 months and 7 pts ≤3 months). A specific gene signature for predicting the onset of hypophysitis has been identified and characterized with 4 genes: IFITM2,CTSS,DUSP1,HLA-B that are mainly involved in the activation of innate-like lymphocyte populations, such as natural killer (NK) cells and innate lymphoid cells (ILCs), and adaptive immune cells, such as T helper 1 (TH1) cells and CD8+ cytotoxic T lymphocytes (CTLs). High gene signature was mostly related to hypophysitis event than lower group (HR: 0.11 95%IC 0.03-0.39, p = 0,0007). Moreover, at data lock all pts who developed hypophysitis were censored with mean overall survival of 35.60 months, 95%CI 30,86-40, 41. Conclusions: A predictive gene signature of hypophysitis was found in melanoma patients treated with adjuvant anti-PD1.Moreover, hypophysitis seems to correlate to better outcome. [Table: see text]