Refractory bullous pemphigoid during treatment with pembrolizumab in the first-line treatment of advanced non-small cell lung cancer

Abstract

Dermatological toxicity is one of the most common immune-related adverse events (irAEs) of treatment with immune checkpoint inhibitors (ICIs). Bullous pemphigoid (BP) is a rare and serious complication of these drugs that can be difficult to establish, as its initial symptoms may be indistinguishable from mild skin lesions. This paper presents the case of a 68-year-old patient who developed BP after receiving one of the ICI therapies, pembrolizumab, for advanced non-small cell lung cancer (NSCLC). After approximately 7 months of therapy, a grade 3 skin toxicity in the Common Terminology Criteria for Adverse Events (CTCAE) occurred in the form of rash and pruritus. Pembrolizumab was then held and prednisone and antihistamines were introduced. When dermal toxicity improved to grade 1, pembrolizumab was resumed and prednisone was kept at a dose of 10 mg. Immunotherapy was discontinued 3 months later, after the recurrence of grade 3 skin toxicity symptoms. When the patient developed blisters filled with clear fluid, dermatologists suspected pembrolizumab-induced bullous pemphigoid. Bullous pemphigoid was subsequently confirmed using a direct immunofluorescence test and histopathological examination. The patient’s skin condition improved after the use of steroid therapy and methotrexate, and the cancer process stabilized for over one year. Cancer progression and deterioration of the patient’s general condition were observed approximately 4 months after the termination of pembrolizumab therapy. The paper also discusses the key aspects of ICIs-induced BP, especially pembrolizumabinduced BP in the first-line treatment of metastatic NSCLC. Early diagnosis of skin lesions and the initiation of appropriate treatment may lead to better outcomes for patients and prevent disruptions in immunotherapy.