Long-term outcomes of chronic immune-related adverse events from adjuvant anti-PD-1 therapy for high-risk resected melanoma

9591 Background: Adjuvant anti-PD1 improves relapse-free survival in high-risk, resected melanoma, but can lead to irAEs, which become chronic in up to 41% of patients (Patrinely et al, JAMA Onc 2021). Given the expanding use of anti-PD-1 in earlier settings in many tumors, it is imperative to assess their long-term effects. We aimed to determine the incidence, characteristics, and long-term outcomes, including resolution vs persistence, of chronic irAEs from adjuvant anti-PD1. Methods: We retrospectively analyzed patients (pts) treated with adjuvant anti-PD1 for resected stage III-IV melanoma from 2015-2022 from 6 institutions; all pts had at least 18 month follow up post-anti-PD1 discontinuation. Demographics, disease characteristics, treatment and recurrence details, and outcomes were collected. Type, grade, duration, treatment, and resolution of acute (onset during treatment) and chronic irAEs (defined as those extending 6+ months after treatment cessation) were characterized. Results: Among 318 pts, 226 (64%) developed acute irAEs arising during treatment, including 44 (20%) with grade 3-5 irAEs. Chronic irAEs developed in 147 (46%) pts, of which 74 (50%) were grade 2+, 6 (4%) were grade 3-5, and 100 (68%) were symptomatic. With long-term follow-up (median 35 months), 52 (35%) pts experienced resolution of chronic irAEs while 95 (30% of the full cohort) had persistent chronic irAEs at last follow-up. Among these 95 pts with persistent chronic irAEs, 43 (45%) were grade 2+, 42 (44%) were symptomatic, 24 (16%) were on steroids, and 42 (29%) were on other management. The most common persistent chronic irAEs were hypothyroid (n = 38), arthritis (n = 18), dermatitis (n = 9), and adrenal insufficiency (n = 8). Of 37 pts with chronic irAEs who received additional immunotherapy, 12 (32%) had a flare, 10 (27%) had no effect, and 20 (54%) had a distinct irAE. Conclusions: In this large cohort of anti-PD1 treated pts, chronic irAEs were common (46%) and frequently were persistent with long-term follow up (30%, most often hypothyroid and arthritis). Prolonged monitoring and management are needed for these long-term survivors. [Table: see text]