1138P Delayed immune-related adverse events (irAEs) on anti-PD1-based therapy

IrAEs typically occur within 4 months of starting anti-PD1-based therapy (anti-PD1 +/- anti-CTLA4), but there are isolated reports of delayed irAEs (onset >12 months after commencement). This study describes the incidence, nature and management of delayed irAE in melanoma patients (pts). Pts from 20 centres with delayed irAEs were studied. The incidence of delayed irAEs was estimated as a proportion of melanoma pts treated with anti-PD1-based therapy and surviving >1yr. irAE onset, clinical features, management and outcomes were examined. 122 pts developed a total of 144 delayed irAEs (23 after initial combination anti-PD-1 with anti-CTLA-4); with an estimated incidence of 5.7% (95% CI 4.3-7.3, 57/999 pts at sites with complete data). The median duration of therapy was 17.7 months (range 0.7-56.0), and median onset of delayed irAE was 16.3 months (range 12.0-53.2). 74% (90 pts) were on anti-PD1 at irAE onset, 12% (15 pts) were <3 months from last dose, 14% (17 pts) were >3 months from last dose of anti-PD1. The most common delayed irAEs were colitis, rash and pneumonitis (Table); 16% (19 pts) had multiple delayed irAEs, 39% (56 irAEs) were ≥G3. Steroids were required in 66% (81 pts), as well as an additional immunosuppressive agent in 23% (28 pts). There were 2 irAE-related deaths; encephalitis with onset during anti-PD1 and a multiple organ-irAE (colon, liver, kidney, lung and haem irAE) with onset 11.4 months after ceasing anti-PD1. Early irAEs (<12 months) had also occurred in 60% (73 pts), affecting a different organ to delayed irAEs in 86% (63 pts).Table: 1138PDelayed irAETotal patientsG1/G2G3/G4G5N (%) requiring systemic corticosteroidsN (%) requiring additional immunosuppressionTOTAL no pts with 144 irAE1227446281 (66%)28 (23%)Colitis31 (22%)1318029 (94%)13 (42%)Rash26 (18%)22407 (27%)1 (4%)Pneumonitis18 (13%)162017 (94%)0 (0%)Rheumatological14 (10%)11309 (64%)7 (50%)Hepatitis12 (8%)210010 (83%)2 (17%)Neurological10 (7%)3618 (80%)3 (30%)Hypophysitis7 (5%)5200 (0%)0 (0%)Renal7 (5%)1607 (100%)3 (43%)Other19 (13%)15405 (26%)1 (5%) Open table in a new tab Delayed irAEs occur in a small but relevant subset of pts, are often different to previous irAE, high grade, difficult to manage and can lead to death. Delayed irAEs mostly occur in pts still receiving anti-PD1, such that the risks of irAE need to be weighed against the benefits of continuing treatment in responding pts beyond 1 year, however pts who stopped treatment remained at risk for developing delayed irAE.