Incidence and outcomes of immune checkpoint inhibitor (ICI) rechallenge after ICI pneumonitis: A single-center retrospective study.

2659 Background: Limited evidence is available on the safety and efficacy of immune checkpoint inhibitor (ICI) rechallenge following an immune-related adverse event (irAE). Pneumonitis is a potentially life-threatening irAE, and minimal data is available with regards to outcomes after rechallenge. In this single-center retrospective analysis we analyzed patients who developed ICI pneumonitis and were later rechallenged with an ICI to further investigate incidence patterns and outcomes. Methods: We conducted a manual chart review on a cohort of 69 patients with ICI pneumonitis at our institution from 2015 to 2024. Rechallenged cases were defined as any patient who developed ICI pneumonitis and were later trialed on the same or another ICI. Patient records were reviewed to identify demographics, clinical features, treatment, and outcomes. Results: Of 69 patients with ICI pneumonitis, we identified 19 that were rechallenged with an ICI. Of these, 10 were women and 9 were men. The average age was 64 years (range: 42-82). Most patients had lung cancer (42%, 8/19) followed by melanoma (32%, 6/19). The treatment intent was palliative for 74% of patients (14/19). The most common therapy was nivolumab (n = 15), however, pembrolizumab, atezolizumab, and durvalumab were also used. The initial grade of ICI pneumonitis was as follows: grade 1 (n = 2), grade 2 (n = 13), grade 3 (n = 3), and grade 4 (n = 1). Many of these patients were treated with steroids, with the average time on steroids being 136 days (range: 0-488). Additionally, the only grade 4 patient was also treated with infliximab due to steroid-refractory pneumonitis. After recovery from their pneumonitis, all patients, except for two, were rechallenged with the same ICI that they had originally been treated with. The average time to rechallenge was 149 days (range: 12-714). Ultimately, 6/19 (32%) patients had recurrent ICI pneumonitis after rechallenge, but all six eventually recovered. On grading ICI toxicity after recurrence, 60% (4/6) remained grade 2, one was downgraded from grade 3 to 2, and one escalated from grade 2 to 3. Eleven percent (2/19) of patients developed an irAE other than pneumonitis (e.g. colitis, arthritis) after rechallenge. Finally, none of the 19 patients died from complications associated with ICI therapy. Conclusions: The recurrence rate of ICI pneumonitis after ICI rechallenge was 32%. At initial presentation, most of these patients had lower grade (grade 1: 2/19, grade 2: 13/19) ICI pneumonitis and most cases of recurrent pneumonitis remained at their initial grade 2. These results indicate that resuming ICI therapy could be considered in select patients with mild to moderate pneumonitis. Further research is needed to investigate immunotherapy rechallenge as it remains a nuanced decision that involves assessing the potential benefits of continued tumor control against the risk of a life-threatening toxicities.