A review of bullous pemphigoid associated with PD‐1 and PD‐L1 inhibitors

BACKGROUND: Dermatologic toxicity represents a substantial portion of all immune-related adverse events (irAEs) associated with PD-1/PD-L1 inhibitors. Bullous pemphigoid (BP) is a rare cutaneous side effect of these medications, which can initially be clinically indistinguishable from other, low-grade cutaneous toxicity. OBJECTIVE: To better characterize the clinical features of BP associated with PD-1/PD-L1 inhibitors, evaluate the efficacy of various treatment regimens, determine the frequency of prodromal pruritus, and assess whether immunological diagnostic studies for BP are warranted in patients treated with checkpoint inhibitors who develop intractable pruritus. METHODS: A comprehensive review of the English-language medical literature was performed using key terms. Papers published on any date and from all origins were considered. Fourteen publications, containing 21 patient cases, were selected independently by two reviewers and deemed relevant to the present publication. RESULTS: Pruritus was a prominent feature of the majority (12/21) of cases and preceded or occurred concurrently with BP development. Bullae developed within 6-8 months of initiation of PD-1/PD-L1 inhibitors; however, a smaller subset of patients did not develop bullae for 1-1.5 years following initiation of therapy. Mean time to pruritus was similar for pembrolizumab and nivolumab at 19 and 21 weeks, respectively. Development of BP required discontinuation of immunotherapy in 76% (16/21) of cases. CONCLUSION: Prodromal or "non-bullous" variants of BP must be considered in patients treated with checkpoint inhibitors who develop protracted or worsening pruritus. Early diagnostic immunological evaluation of the skin may lead to improved patient outcomes by facilitating timely initiation of treatment and prevent disruptions in cancer therapy.