Effect of glucocorticoids for the management of immune-related adverse events on outcome in melanoma patients treated with immunotherapy – a retrospective and biomarker study

Abstract

Immune-related adverse events (IRAEs) during therapy with immune checkpoint-inhibitors (ICIs) are common, and its management sometimes requires glucocorticoids (GC). Predictors for development of IRAEs and data about the impact of GC on clinical outcome are missing. We evaluated the impact of GC to treat IRAEs on clinical outcome, and plasmatic inflammatory proteins as predictors for IRAEs.Patients with melanoma (n=98) treated with ICIs at Karolinska University Hospital were included. Clinical information and data regarding prescription of systemic GC were collected. Baseline plasma samples (n=57) were analyzed for expression of 92 inflammatory proteins.Forty-four patients developed at least one IRAE requiring systemic GC and the most common was hypocortisolemia (n=11). A median overall survival (mOS) of 72.8 months for patients developing IRAEs requiring GC, 17.7 months for those who did not, and 1.4 months for individuals receiving GC at baseline was observed in Kaplan-Meier curves (p = 0.001). In immortal time bias adjusted analysis patients receiving steroids to treat IRAE survived slightly longer, even though this time trend was not statistically significant. The mOS was 29 months for those treated with GC within 60 days after ICIs start and was not reached for patients receiving GC later. The number of ICIs cycles was higher in subjects receiving GC after 60 days (p=0.0053). Hypocortisolemia occurred mainly in males (10/11) and correlated with favorable outcome. Male patients with hypocortisolemia had lower expression of IL8, TGF-alfa and FGF5 and higher expression of DNER.GC may be used to treat IRAEs without major concern. However, GC early during ICIs may impact clinical outcome negatively. The prognostic value of hypocortisolemia and inflammation proteins as biomarkers should be further investigated.