1168 Rare and serious skin toxicity of immune-checkpoint inhibitors: a focus on bullous dermatosis and SJS/TEN

<h3>Background </h3> While cutaneous adverse events (CAE) may occur in 30–50% of patients on immune checkpoint inhibitors (ICIs), immunobullous eruptions occur in only 1% of patients. Other severe CAEs are even more uncommon, therefore, characterization of these often-fatal cutaneous toxicities remain poor. <h3>Methods</h3> MRNs of patients who developed severe CAE while on ICI were retrospectively reviewed to abstract information including demographics, diagnosis, treatment, details of serious dermatologic adverse events and their impact on anti-neoplastic therapy. <h3>Results</h3> Of 1,900 patients in our dataset, 5 experienced serious (CTCAE v.5) grade ≥2 bullous CAEs. Median age was 74 years (63–88 y), 4 were male and all were white. Primary cancer diagnoses were melanoma for 4 and renal cell carcinoma in 1 patient. 80% (n=4) received ICI as palliative therapy. 80% received radiation therapy. 4 patients (80%) developed bullous dermatitis (BD) and 1 (20%) developed SJS/TEN overlap syndrome. 4 (80%) patients received anti-PD1 alone and 1 (20%) received combination anti-CTLA4 plus anti-PD1. All patients presented with a prodrome of diffuse, pruritic macular-maculo-papular rash. Other common presenting symptoms included mild elevation in eosinophils (80%) and mild transaminitis (60%). Median time from ICI initiation to SJS/TEN and BD was 38 days (from combination ICI therapy) and 560.5 days, respectively. Dermatology consultation was obtained in 5 and a skin biopsy was obtained in 3 patients. Patient with SJS/TEN required ICU admission, oral steroids and cyclosporine, and died 5 days after hospitalization. 3/4 patients with BD underwent a skin biopsy, and 2/4 showed positive direct immunofluorescence. 2/4 patients with BD received outpatient treatment with topical steroid, 1 additionally with niacinamide and minocycline. 2/4 patients required hospitalization for a median of 7 days. Both hospitalized patients received oral steroids, topical clobetasol, niacinamide and doxycycline. 1 required mycophenolate initiation without clinical improvement. 2 patients completed ICI therapy. Therapy was permanently discontinued in 3. ICI led to stable disease in 2/5 patients and partial remission in 2/5 patients at the time of serious CAE. 2 patients were still living at the time of last contact. Median survival from irAE onset for the other 3 patients was approximately 137 days. Cause of death was irAE in 1, disease progression in 1 and other in 1 patient. <h3>Conclusions</h3> Severe CAEs may manifest anywhere from weeks-years after ICI initiation. Patients developed a prodromal pruritic macular-maculo-papular rash prior to more severe cutaneous reaction. Timely clinical assessment of patients with maculo-papular rash on ICI therapy is warranted for early intervention. <h3>Ethics Approval</h3> The study was approved by UVA IRB HSR (Study 24436).