84 Background: Anti-PD-1/PD-L1 immune checkpoint inhibitors (ICIs) for cancer may cause immune-related adverse events (irAEs). Large clinical trials and meta-analyses have identified the spectrum of single organ-specific irAEs that may occur with these agents. However, patients treated with these agents may develop irAEs involving multiple organ systems. The prevalence and clinical patterns of multi-system irAEs and their management have yet to be elucidated. Methods: Patients with lung cancer treated with either PD-1/PD-L1 monotherapy or PD-1/PD-L1-based combinations at Johns Hopkins Hospital were identified. Clinical, radiologic and pathologic data were stored in an IRB-approved database. irAEs were identified through retrospective chart review and confirmed by a multidisciplinary team. Multi-system irAEs were defined as irAEs in +1 organ system. Patients with multi-system irAEs, their clinical patterns, management and outcomes were identified. Results: 319 patients were identified (NSCLC: 299, 93.7%; SCLC: 20, 6.3%) and received treatment with either PD-1/PD-L1 monotherapy (197, 61.8%) or combinations (122, 38.2%: + chemotherapy = 42; +immunotherapy = 41; +other = 39). Of these patients, 77 (24.1%) developed 1 irAE, and 16 (5%) developed multi-system irAEs (2 irAEs: 14; 3 irAEs: 2). The most common irAEs were pneumonitis (42, 13.2%), dermatitis (11, 3.4%), and hypothyroidism (9, 2.8%). The most common multi-system irAEs was pneumonitis/dermatitis (3, 3.9%). Patients who developed dermatitis, colitis, or hypothyroidism were most likely to develop multi-system irAEs (all p < 0.05). Management and outcome data for individual and multi-system irAEs will be presented. Conclusions: Patients treated with ICIs may develop multi-system irAEs. In the first report of this clinical entity, we identified that 5% of lung cancer patients treated with PD-1/PD-L1 developed multi-system irAEs, and that those who developed dermatitis, colitis, or hypothyroidism were most likely to develop multi-system events. These data have important implications for interdisciplinary patient management in the era of cancer immunotherapy.