Oral upadacitinib for the management of refractory immune checkpoint inhibitor-induced lichenoid reaction

Summary: Abstract Body: Severe cutaneous immune-related adverse events (cirAEs) often necessitate steroids and biologics. Some cases, however, remain recalcitrant to these systemic treatment modalities. Janus kinase inhibitors (JAKi) are approved for various inflammatory disorders and represent another promising therapeutic option in these instances. A 79-year-old woman with metastatic renal cell carcinoma initially presented with a grade 1 pruritic, papular eruption involving the face, chest, back, and legs starting a few days after her first and only infusion of ipilimumab and nivolumab. Despite treatment with topical steroids and antihistamines, the rash rapidly worsened to a grade 3 erosive lichenoid eruption over 4 days with greater than 90% body surface area involvement. The patient remained afebrile and experienced no new systemic symptoms, such as arthralgia or myalgia. Punch biopsy confirmed lichenoid dermatitis and laboratory findings showed an ANA titer of 1:320, elevated IL-5 and IL-6, and negative SSA/Ro. Following continual worsening of the eruption despite a prolonged course of prednisone, three doses of dupilumab, as well as apremilast 30 mg BID, oral upadacitinib (15 mg daily) was initiated. Within one week, the patient experienced dramatic resolution of the rash with only mild erythema remaining. She is currently not planned for ICI rechallenge. Systemic JAKi have demonstrated efficacy in managing ICI-related hepatitis, myocarditis, and colitis. Although JAKi should be used with caution in all patients, including those with malignancy, they exhibit a favorable safety profile in cancer patients with irAEs and exert a synergistic effect with checkpoint blockade in patients with Hodgkin lymphoma according to a phase I clinical trial. Our case highlights the potential therapeutic promise JAKi have as a steroid-sparing option for severe cirAEs. Viviane Liao¹, Yingjoy Li¹, Klaus J. Busam², Lavanya Mittal¹ 1. Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States. 2. Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States. Clinical Research: Interventional Research