Immuno-oncologyDupilumab for bullous pemphigoid related to immune checkpoint inhibitors: a retrospective case series

Abstract

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but are associated with treatment-limiting immune-related cutaneous adverse events (irCAEs). Immune checkpoint inhibitor-related bullous pemphigoid (irBP), a severe, blistering irCAE occurs in 0.3%-1.5% of patients receiving ICI therapy. While systemic steroids can be effective, they are associated with significant toxicity and may mitigate -immunotherapy antitumor efficacy. Consequently, steroid-sparing therapies are needed. Dupilumab, an IL-4 and IL-13 receptor antagonist, has demonstrated efficacy in non-ICI-related BP and appears promising for managing irBP.

Methods: We conducted a retrospective review of patients treated with dupilumab for irBP from April 2020 to April 2024. Clinical data, outcomes, and adverse events were assessed. Inhibitor-related bullous pemphigoid response was categorized as complete response (CR), partial response (PR), or no response (NR).

Results: In all, 17 patients (59% male, 82% non-Hispanic White; mean age 72.7 years) developed irBP while receiving PD-1/PDL-1 inhibitors. Sixteen patients (94%) received dupilumab for active irBP and one (6%) for prevention of recurrence. Dupilumab achieved CR of irBP for 12 patients (75%) and PR for 2 (12%) patients with active irBP. Ten (62%) achieved CR with dupilumab systemic monotherapy. Median time to first response was 19.5 days (range = 3-50). Most patients with CR (58%) failed prior oral corticosteroid therapy. The patient treated prophylactically experienced no irBP recurrence. Dupilumab was well-tolerated, with no adverse events.

Conclusions: Dupilumab is a promising steroid-sparing option for irBP, achieving initial response in under 20 days for most cases. Dupilumab is a valuable tool to manage this challenging irCAE while minimizing risk related to systemic steroid treatment.

Keywords: ICI; bullous pemphigoid; dupilumab; immunotherapy; oncodermatology; toxicity.

Figure 1.

Biopsy demonstrating subepidermal vesiculobullous dermatitis with eosinophilic infiltrate in sample from PIDN10 (A). Direct immunofluorescence (DIF) findings demonstrating linear immunoglobulin (IgG) at the dermo-epidermal junction (B). This sample was also demonstrated linear IgG4 and C3 at the dermo-epidermal junction (not pictured).

Figure 2.

Swimmer plot of immune checkpoint inhibitor-related bullous pemphigoid (irBP) response to dupilumab treatment. Patients are ordered by latest date of immune checkpoint inhibitors (ICI) therapy. Immune checkpoint inhibitor therapies are coded based on the colors in the legend. Dates of bullous pemphigoid symptoms are represented by the black bar and dates of treatment with systemic agents including biologics other than dupilumab, dupilumab, and steroids are indicated by the small colored bars. Immune checkpoint inhibitor-related bullous pemphigoid response to dupilumab therapy is indicated with CR corresponding to complete response of irBP, PR to partial response, NR to no response, and no recurrence corresponding to the patient given dupilumab prophylaxis to prevent recurrence of bullous pemphigoid symptoms.

Figure 3.

Clinical photos of immune checkpoint inhibitor-related bullous pemphigoid (irBP) response to dupilumab treatment. Patient ID2 (PID2) 1 month before initiating dupilumab treatment (A) and 3 months after treatment start (B), demonstrating PR of irBP. The patient went on to achieve complete recovery (CR). Patient ID3 (PID3) 1 month before start of dupilumab (C) and demonstrating CR 6 months after dupilumab initiation (D). Patient ID11 (PID11) 20 days before dupilumab (E) and exhibiting PR to dupilumab after 3 months of treatment (F). PID11 achieved CR 9 months later. Patient ID11 (PID13) at first presentation for irBP (G) and exhibiting CR four months after starting dupilumab (H).