Bterrani Elie S, Kamar Francois G
Division of Hematology-Oncology, Department of Medicine, Univeristy of Balamand, School of Medicine, Balamand, Lebanon.
Hematology-Oncology Division, Department of Internal Medicine, Mount Lebanon University Medical Center, Hazmieh, Lebanon.
Discov Oncol. 2025 Jul 1;16(1):1195. doi: 10.1007/s12672-025-02377-7.
Pembrolizumab, a PD-1 inhibitor, is widely used for treating advanced cancers, including metastatic non-small cell lung cancer (NSCLC). However, its use can lead to immune-related adverse events (IRAEs), including cutaneous manifestations such as bullous pemphigoid (BP).
We report a case of a 69-year-old gentleman with metastatic left lung adenocarcinoma who developed steroid-resistant BP following pembrolizumab treatment. Initially diagnosed in August 2020 and treated with surgery, chemotherapy, and an IL-1B inhibitor, the patient showed no evidence of recurrence until November 2021. Subsequent metastases were treated with surgery, stereotactic radiosurgery (SRS), and whole-brain radiotherapy (WBRT). In November 2022, pembrolizumab was initiated. Following three sessions, the patient developed facial skin edema, muscle weakness, and later, a rash with multiple bullae. Despite discontinuing pembrolizumab and starting high-dose topical steroids and oral prednisone, the BP proved to be refractory. The patient was switched to methotrexate with marked improvement but not complete resolution. Continued management included reduced pembrolizumab doses and additional SRS, eventually achieving control over both the metastatic disease and BP.
This case highlights a case of severe and steroid-resistant nature of pembrolizumab-induced BP, necessitating alternative immunosuppressive therapy. The complexity of managing IRAEs in patients undergoing ICI therapy underscores the importance of a multidisciplinary approach and vigilant monitoring.
This report adds to the growing body of evidence on IRAEs, particularly BP induced by ICIs, and suggests that methotrexate can be an effective treatment for steroid-resistant BP in the context of cancer immunotherapy. Further research is needed to better understand the mechanisms and optimal management strategies for ICI-induced BP.
帕博利珠单抗是一种PD - 1抑制剂，广泛用于治疗晚期癌症，包括转移性非小细胞肺癌（NSCLC）。然而，其使用可能导致免疫相关不良事件（IRAEs），包括大疱性类天疱疮（BP）等皮肤表现。
我们报告一例69岁患有转移性左肺腺癌的男性患者，在接受帕博利珠单抗治疗后出现了对类固醇耐药的BP。该患者最初于2020年8月被诊断出，并接受了手术、化疗和一种IL - 1B抑制剂治疗，直到2021年11月均未发现复发迹象。随后的转移瘤接受了手术、立体定向放射外科（SRS）和全脑放疗（WBRT）治疗。2022年11月开始使用帕博利珠单抗。在三个疗程后，患者出现面部皮肤水肿、肌肉无力，随后出现伴有多个大疱的皮疹。尽管停用了帕博利珠单抗并开始使用高剂量外用类固醇和口服泼尼松，但BP被证明具有耐药性。患者改用甲氨蝶呤后有明显改善，但未完全缓解。持续的治疗包括减少帕博利珠单抗剂量和额外的SRS，最终实现了对转移性疾病和BP的控制。
本病例突出了帕博利珠单抗诱导的BP具有严重且对类固醇耐药的性质，需要替代免疫抑制疗法。在接受免疫检查点抑制剂（ICI）治疗的患者中管理IRAEs的复杂性强调了多学科方法和密切监测的重要性。
本报告增加了关于IRAEs，特别是ICI诱导的BP的证据，并表明在癌症免疫治疗的背景下，甲氨蝶呤可以是治疗类固醇耐药BP的有效方法。需要进一步研究以更好地理解ICI诱导的BP的机制和最佳管理策略。
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