Dupilumab for bullous pemphigoid induced by immune checkpoint inhibitors.

Abstract

e24110 Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but are associated with treatment-limiting immune-related cutaneous adverse events (irCAEs). ICI-associated Bullous pemphigoid (irBP), a severe, blistering irCAE occurs in 0.3–1.5% of patients receiving ICI therapy. While systemic steroids can be effective, long courses may be required, which are associated with significant toxicity and may mitigate the antitumor effect of immunotherapy. Consequently, identification of steroid-sparing therapies is crucial. Dupilumab, an IL-4 and IL-13 receptor antagonist, has shown efficacy in non-ICI related BP and has emerged as a promising therapy for ICI-induced BP. Objective: This study evaluated the efficacy of dupilumab in managing ICI-induced BP at a tertiary cancer center. Methods: We conducted a retrospective review of all patients treated for ICI-induced BP with dupilumab from April 2020 to April 2024, yielding a cohort of 17 patients. Clinical data, treatment responses, and outcomes were assessed. Response of ICI-induced BP were categorized as complete response (CR), partial response (PR), or no response (NR). Results: 17 patients (59% male, 82% non-Hispanic White) with a mean age of 72.7 (SD=11) years developed BP while receiving PD-1/PDL-1 inhibitors: pembrolizumab (65%), nivolumab (24%), dostarlimab (6%), and cemiplimab (6%). All patients were treated with a loading dose of 600mg followed by 300mg subcutaneously biweekly. Sixteen patients (94%) received dupilumab for treatment of active BP and one patient (6%) for prevention of BP recurrence. Treatment with dupilumab for BP achieved CR for 12 patients (75%) with active BP, with 10 (62%) achieving CR with dupilumab as the only active systemic agent at a median time of 110.5 days (range=21-336). Two patients achieved CR with dupilumab combined with systemic corticosteroids. PR was achieved in two patients (12%) with active disease, while two patients (12%) showed NR. For patients with PR or CR, the median time to first response was 19.5 days (range= 3-50) and median time to best response was 109.5 days (range=3-366). Most patients with CR (58%) had failed prior corticosteroid therapy. Dupilumab was well-tolerated, with no reported adverse events. Finally, the patient receiving dupilumab to prevent BP recurrence while on ICI therapy developed no further BP symptoms. ICI treatment was held in 7 patients (41%) upon BP development, and two of these patients were able to restart immunotherapy concurrently with dupilumab. Ten patients (59%) continued ICI therapy despite BP. Conclusions: Dupilumab shows promise as a steroid-sparing option for ICI-induced BP, achieving CR for ICI-induced BP in most cases under 200 days. Further prospective studies are needed to confirm efficacy and explore prophylactic use. Dupilumab is a valuable tool to manage this challenging irCAE while minimizing risk related to the use of systemic steroids.