Abstract 5818: Incidence and management of steroid-refractory immune checkpoint inhibitor pneumonitis: a single-center retrospective analysis

Abstract Introduction: Pneumonitis is a serious and potentially lethal complication of treatment with immune checkpoint inhibitors (ICI). In a rare subset of patients, front-line treatment with steroids is ineffective, necessitating a second-line steroid-sparing agent. We conducted a single-center, retrospective analysis of patients treated with ICIs to determine incidence and outcome patterns of patients who develop pneumonitis. Methods: We conducted manual chart review on a cohort of 2, 820 patients treated with ICIs at our institution from 2015 to 2024. Steroid-refractory pneumonitis was defined as no clinical improvement between 48 hours and up to 14 days after initiation of high-dose corticosteroids. Electronic medical records were then reviewed to identify the clinical features at presentation and overall outcomes. Results: Of 2, 820 patients, we identified 69 with ICI pneumonitis and 11.6% (8/69) with steroid-refractory ICI pneumonitis. The mean age was 69.5 years (range: 42-91) and 53.6% were female (37/69). Most patients had lung cancer (53.6%, 37/69) followed by both renal cancer and melanoma (both: 13%, 9/69), with the treatment goal being palliative for 79.7% (55/69). The mean number of ICI treatments before steroid-refractory ICI pneumonitis diagnosis was 5, compared to 12 for all patients with pneumonitis. Diffuse alveolar damage (DAD) was the most common radiologic pattern amongst steroid-refractory cases (5/8, 62.5%). After corticosteroid failure, patients were managed with: infliximab (n=1), mycophenolate (n=1), a combination of IVIG and infliximab (n=1), no second-line agent in lieu of a longer steroid course (n=1), or hospice alone (n=4); 3/8 (37.5%) required ICU-level of care, 7/8 (87.5%) required some form of oxygen supplementation (ranging from nasal cannula to noninvasive positive pressure ventilation). Ultimately, 6/8 (75%) patients died from steroid-refractory ICI pneumonitis. The patient that received infliximab alone recovered from his pneumonitis but ultimately died from cancer progression. The patient that elected a longer steroid course had recurrent pneumonitis after steroid taper but eventually recovered. Conclusions: Steroid-refractory ICI pneumonitis is uncommon, only affecting 11.6% of ICI pneumonitis cases at our institution, however, it is responsible for significant mortality. As seen in other studies, steroid-refractory ICI pneumonitis occurred early in ICI treatment. After corticosteroid failure, only 3/8 patients were treated with a second immunosuppressant agent, indicating second-line immunosuppressants may be underutilized in this population. Little data has been generated on outcomes of patients treated with high-dose steroids without second-line therapy. There is a significant need for prospective, randomized trials to determine the best treatment strategies for this patient population. Citation Format: MacKenzie Adams, Charmi Trivedi, Sapana Gupta, Jacqueline Chu, Curtis Petruzzelli, Kanika Malani, Rebecca Steuer, William Park, Sathwik Madireddy, Sandeep Jain, Benedito Carneiro, Matthew J. Hadfield. Incidence and management of steroid-refractory immune checkpoint inhibitor pneumonitis: a single-center retrospective analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5818.