Safety outcomes of intravenous immunoglobulin (IVIG) in treatment of steroid-refractory immune-checkpoint inhibitor pneumonitis.

2666 Background: Pneumonitis is a potentially severe adverse event of immune checkpoint inhibitors (ICIs). While the first line treatment for ICI pneumonitis is corticosteroids, there are subsets of patients who either fail to respond, deemed steroid-refractory, or who cannot be tapered off steroids, deemed steroid-dependent. In these patients, there is no clear consensus on the best approach to treatment. IVIG has emerged as a potentially efficacious treatment for its immunomodulatory effects. It is also less immunosuppressive than other potential therapies, which is beneficial in a population which respiratory infection could lead to rapid clinical decline. However, there are concerns about treatment safety, including volume overload, thrombosis, and renal injury, which can be devastating in a patient population with pre-existing respiratory compromise. In this study, we aimed to assess the safety of IVIG treatment in patients with steroid-refractory ICI pneumonitis. Methods: A retrospective review was conducted of patients with steroid-refractory ICI pneumonitis treated with IVIG at Johns Hopkins Hospital from 2018 to 2024. Patient characteristics, treatment features, disease severity, clinical outcomes, and development of adverse events post-IVIG including renal injury, volume overload, or thrombosis were evaluated. Results: A total of 31 patients were selected with steroid refractory pneumonitis treated with IVIG. Mean age at diagnosis was 68 (56-80). The most common primary tumor site was lung (n = 23) and majority of patients had stage IV malignancy (n = 19). 81% (25/31) had grade 3 or 4 pneumonitis at the time of IVIG therapy. In-hospital death occurred in 41% (13/31). Majority of in-hospital death was due to respiratory decompensation from pneumonitis and no deaths were directly related to complications of IVIG. Regarding adverse events, 9.68% (3/31) of patients developed a venous thromboembolism related to IVIG. 3.23% (1/31) developed acute kidney injury and 12.90% (4/31) developed hypervolemia in response to IVIG. Conclusions: IVIG was not associated with a high rate of toxicity when used in the treatment of steroid refractory ICI-pneumonitis. The increased in-hospital mortality indicates the severity of illness in this patient population. Despite this, IVIG-related adverse events were low overall. Although a small cohort, these results suggest a favorable safety profile and support further study to evaluate efficacy of IVIG as compared with other immunomodulatory agents. IVIG treatment related adverse events. VTE related to IVIG* (%; n) 9.68 (3) Acute kidney injury (%; n) 3.23 (1) Volume overload (%; n) 12.90 (4) IVIG: intravenous immunoglobulin, VTE: venous thromboembolism. *2 of the patients died.