1152P Association of immune-related adverse events (irAE) requiring glucocorticoids (GCs) with outcome and biomarkers in advanced cutaneous malignant melanoma (CMM) treated with immune checkpoint inhibitors (ICI)

Therapy with ICIs have been successful with long-term survival benefits for some CMM patients. However, ICIs may also cause irAEs which could be serious and demand the prescription of GC. The combination of ICIs improves treatment efficacy but increases the risk for irAEs. The impact of GC treated irAE (GC-irAE) on efficacy of ICIs is not fully understood and biomarkers assessing the risk for irAE requiring GC treatment are not available. We studied a cohort of patients with metastatic CMM treated with ICI to evaluate if GC-irAE impact clinical outcome. We also investigated whether inflammation proteins in baseline plasma samples may predict the development of GC-irAE. This is a cohort study performed at Karolinska University Hospital in Sweden including 98 subjects with advanced CMM (M1a-d), who received anti-PD1 alone (n=88), anti-PD1+ epacadostat (clinical trial, n=3) or ipilimumab + nivolumab (n=8) as 1st line therapy in most cases (85%). Clinical data regarding the use of GC to treat irAE were collected retrospectively. If GC-irAE occurred, the type of irAE was assembled. Baseline plasma samples from 58 of the 98 patients were analyzed utilizing the OLINK inflammation protein panel platform. In the whole cohort 65% were male and median age was 70 years. The median PFS and OS for the whole cohort were 12 and 38 months, respectively. Of 98 patients 44% developed GC-irAE. The most common GC-irAE were hypophysitis (11%), dematitis (7%), colitis (7%) and pneumonitis (6%). The median time to GC treatment start after ICI therapy was 146 days. The median PFS and OS for GC-irAE vs patients without GC-irAE were 24 and 73 months vs 5 and 18 months, respectively. Patients developing hypophysitis had a longer OS compared to other patients. High baseline levels of IL8 and S100A12 were associated with worse OS and high levels of DNER was associated with better OS and with risk of developing hypophysitis. Patients developing a GC-irAE had significantly increased PFS and OS compared to the other patients. Further studies on potential biomarkers for risk of developing hypophysitis are warranted to timely avoid serious complications.