A 63-year-old man with stage IVb squamous cell lung carcinoma (PD-L1 <1%) and brain metastases received carboplatin, nab-paclitaxel, and pembrolizumab following surgical resection of intracranial disease and whole-brain radiotherapy. After 10 months of systemic therapy, he developed severe bullous pemphigoid with extensive tense bullae, erosions, and debilitating pruritus (Fig. 1A, BPDAI score 96). Skin biopsy confirmed subepidermal blistering with eosinophilic infiltrate, and serology revealed markedly elevated anti-BP180 antibodies (>200U/mL). Initial treatment with high-dose corticosteroids and mycophenolate mofetil allowed clinical stabilization; however, pembrolizumab rechallenge triggered severe relapse with widespread bullous eruption, necessitating permanent immunotherapy discontinuation and prolonged hospitalization. Addition of omalizumab ultimately achieved disease control. Remarkably, over eight months without active oncologic therapy, chest CT demonstrated progressive regression of the right upper lobe tumor and stable contralateral disease (Fig. 1B), with corresponding metabolic reduction on PET-CT (SUVmax from 27.4 to 5.0). This case illustrates that severe, corticosteroid-refractory immune-related adverse events – though necessitating permanent immunotherapy withdrawal – may paradoxically signal robust immune activation with durable antitumor responses [1–5]. The images highlight the clinical complexity of managing life-altering immunotherapy toxicity while maintaining prolonged tumor control through immune memory mechanisms, emphasizing that treatment discontinuation does not invariably portend disease progression and may reflect successful immune priming rather than therapeutic failure [1–5].

Fig. 1.

(A) Evolution of dermatological lesions between May (left) and September (right) of 2024. (B) Evolution of primary pulmonary lesion between March 2023 (left), before treatment, and February 2025 (right), 5 months wihout pembrolizumab.