Case Report: Autoimmune Pemphigus Vulgaris in a Patient Treated With Cemiplimab for Multiple Locally Advanced Cutaneous Squamous Cell Carcinoma

No systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma.

Immune checkpoint antibodies that augment the programmed cell death protein 1 (PD-1)/PD-L1 pathway have demonstrated antitumor activity across multiple malignancies, and gained recent regulatory approval as single-agent therapy for the treatment of metastatic malignant melanoma and nonsmall-cell lung cancer. Knowledge of toxicities associated with PD-1/PD-L1 blockade, as well as effective management algorithms for these toxicities, is pivotal in order to optimize clinical efficacy and safety. In this article, we review selected published and presented clinical studies investigating single-agent anti-PD-1/PD-L1 therapy and trials of combination approaches with other standard anticancer therapies, in multiple tumor types. We summarize the key adverse events reported in these studies and their management algorithms.

Pemphigus consists of a group of rare and severe autoimmune blistering diseases mediated by pathogenic autoantibodies mainly directed against two desmosomal adhesion proteins, desmoglein (Dsg)1 and Dsg3 (also known as DG1 and DG3), which are present in the skin and surface-close mucosae. The binding of autoantibodies to Dsg proteins induces a separation of neighbouring keratinocytes, in a process known as acantholysis. The two main pemphigus variants are pemphigus vulgaris, which often originates with painful oral erosions, and pemphigus foliaceus, which is characterised by exclusive skin lesions. Pemphigus is diagnosed on the basis of either IgG or complement component 3 deposits (or both) at the keratinocyte cell membrane, detected by direct immunofluorescence microscopy of a perilesional biopsy, with serum anti-Dsg1 or anti-Dsg3 antibodies (or both) detected by ELISA. Corticosteroids are the therapeutic mainstay, which have recently been complemented by the anti-CD20 antibody rituximab in moderate and severe disease. Rituximab induces complete remission off therapy in 90% of patients, despite rapid tapering of corticosteroids, thus allowing for a major corticosteroid-sparing effect and a halved number of adverse events related to corticosteroids.