Delayed Toxicities With Anti-Pd-1 And Anti-Pdl-1 Immune Checkpoint Inhibitors (Icis)

e15074 Background: ICI use is associated with immune-related adverse events (irAEs). Most irAEs occur early (within 3 months), but data regarding late toxicities is not well reported. Methods: Patients (pts) treated with ICIs (nivolumab [PD-1], pembrolizumab [PD-1], or atezolizumab [PDL-1]) were identified from pharmacy records across MedStar Health Network hospitals. The CTCAE 4.03 grading system was used to define irAEs. Pts who received distinct ICIs at separate time points were considered as separate events. We defined delayed toxicities as irAEs that developed 1 year after the first dose of ICI either on or off treatment (pts who did not receive subsequent therapies). Pts in whom irAEs developed during or after subsequent therapies were excluded from analysis. Results: We identified 325 pts who received 328 ICI therapies. 26% (n = 59) of pts developed any grade (grd) irAEs, with 8% (n = 26) of pts developing grd ≥3 irAEs. Of irAEs, 55% (n = 73) occurred within 3 months, 35% (n = 47) in between 3 to 12 months and 10% (n = 13) after 12 months. Of delayed irAEs, 46% (n = 6) of pts were on ICIs and 54% (n = 7) were off ICIs at the time of irAE onset. In the off treatment delayed irAE cohort, 70% of pts developed grd ≥2 irAEs, including colitis (grd 3, n = 1), joint pain (grd 3, n = 1), neurological toxicity (grd 2, n = 1), mucositis (grd 3, n = 1), and hypothyroidism (grd 2, n = 1). Of this cohort, five pts required systemic steroids. irAEs resolved within two weeks except one case in which colitis took 6 months to resolve. 12% (n = 40) of pts continued ICIs beyond 1 year, in which 15% (n = 6) developed delayed irAEs. These delayed irAEs were joint pain (grd 1, n = 1), pruritis (grd 1, n = 1), rash (grd 2, n = 1), hypothyroidism (grd 1, n = 1), hyponatremia (grd 1, n = 1) and colitis (grd 3, n = 1). Colitis required systemic steroid use and took 6 weeks to resolve, after which ICI was discontinued. In the pt with grd 2 rash, treatment with ICIs was continued. Conclusions: Findings from our retrospective study suggest that 15% of pts who continue ICIs beyond 1 year are at risk of developing delayed irAEs, which may require chronic immunosuppressive therapy. Delayed irAEs should be considered in discussions about treatment cessation in pts with major responses to ICIs.