Cutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma: A single-institution cohort

Hwang, Shelley Ji Eun; Carlos, Giuliana; Wakade, Deepal; Byth, Karen; Kong, Benjamin Y.; Chou, Shaun; Carlino, Matteo S.; Kefford, Richard; Fernández‐Peñas, Pablo

doi:10.1016/j.jaad.2015.10.029

Cited by 269 publications

(282 citation statements)

References 26 publications

(38 reference statements)

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“…21 Histologic presentations may also vary, with the lichenoid (or interface) pattern being the most commonly recognized. 22–29 Immunohistochemical analysis of anti-PD-1-induced lichenoid dermatitis shows similarity to idiopathic lichen planus 24 and suggests a T-cell-mediated process, 23 which is consistent with the recognized mechanism of action for these agents.…”

Section: Introductionsupporting

confidence: 62%

Cutaneous Eruptions in Patients Receiving Immune Checkpoint Blockade

Kaunitz¹,

Loss²,

Rizvi³

et al. 2017

American Journal of Surgical Pathology

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Cutaneous eruptions are among the most common immune-related adverse events (irAEs) associated with anti-PD-1/PD-L1 therapy, and are often clinically and histologically characterized as lichenoid. Non-lichenoid patterns may also occur and are likely to be encountered by surgical pathologists, given the increasing clinical use of these agents. The purpose of this study is to describe the histopathologic features of non-lichenoid cutaneous irAEs from patients receiving anti-PD-1/PD-L1 therapies for a variety of underlying advanced malignancies. Sixteen patients with 17 biopsied eruptions were included from two academic institutions with extensive experience administering and monitoring responses to immune checkpoint blockade as well as treating the potential side effects. Eruptions occurred a median of 10 days (range 1 day to 11.4 months) after treatment initiation. Nearly half of specimens demonstrated either a psoriasiform/spongiotic or an urticarial-type reaction pattern on histologic review. Patterns consistent with Grover’s disease, bullous pemphigoid, and granulomatous dermatitis were also observed. Nearly two-thirds of patients required systemic corticosteroids for treatment of the cutaneous irAE, and 19% of patients discontinued immunotherapy due to their skin eruptions. 75% of patients showed an objective antitumor response. The diverse array of non-lichenoid cutaneous irAE presented here should reflect and inform the scope of histologic patterns encountered by the practicing surgical pathologist. Such eruptions are seen in patients with a variety of underlying tumor types, many of whom ultimately demonstrate a favorable response to immune checkpoint blockade.

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Section: Introductionsupporting

confidence: 62%

Cutaneous Eruptions in Patients Receiving Immune Checkpoint Blockade

Kaunitz¹,

Loss²,

Rizvi³

et al. 2017

American Journal of Surgical Pathology

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“…Most toxicities are low grade and are generally effectively managed and reversible with corticosteroids and dose interruptions [7]. Frequently observed cutaneous adverse events associated with anti-PD1 antibodies include lichenoid reactions, eczema and vitiligo [4].…”

Section: Discussionmentioning

confidence: 99%

“…Both agents have been shown to improve survival in metastatic melanoma, with multiple studies ongoing in a broad range of tumour types including renal cell carcinoma and nonsmall-cell carcinoma [2,3]. These agents are associated with the development of immune-related adverse events (irAEs) most commonly affecting the skin, clinically manifesting as lichenoid reactions, eczema and vitiligo [4].…”

Section: Introductionmentioning

confidence: 99%

Bullous pemphigoid, an autoantibody-mediated disease, is a novel immune-related adverse event in patients treated with anti-programmed cell death 1 antibodies

Hwang

Carlos

Chou³

et al. 2016

Melanoma Research

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Anti-programmed cell death 1 (anti-PD1) antibodies such as pembrolizumab have shown improved progression-free and overall survival in patients with advanced melanoma. Of 124 patients reviewed in Westmead Hospital from May 2012 to November 2015, treated with pembrolizumab for advanced melanoma, we encountered three cases of bullous pemphigoid (BP). We have previously reported a case of BP. In two recent cases, BP was diagnosed early and treated promptly with potent topical or oral steroid. Patients on anti-PD1 antibodies are at a higher risk of developing cutaneous immune-related adverse events such as lichenoid reactions, eczema and vitiligo. No cases of BP were encountered in the previously published cohort of 260 melanoma patients treated with BRAF inhibitors; as such, it appears that BP is associated with anti-PD1 treatment rather than metastatic melanoma. BP appears to be another immune-related adverse event, and clinicians should have a low threshold for performing cutaneous biopsies and immunofluorescence studies in patients on anti-PD1 therapies.

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“…1–4 In addition, cutaneous lichenoid reaction has also emerged as one of the most prevalent dermatological toxicities in treated patients. 4–7 In contrast, sparing of oral mucous membranes is often reported and oral lichenoid reactions (OLR) have only been anecdotally described. 4–8 Herein, we describe the clinicopathological features of 10 new cases in Table 1.…”

mentioning

confidence: 99%

Oral lichenoid reactions associated with anti‐PD‐1/PD‐L1 therapies: clinicopathological findings

Sibaud

Eid

Belum

et al. 2017

Acad Dermatol Venereol

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Cutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma: A single-institution cohort

Abstract: Anti-PD-1 therapy is associated with the development of immune-related cutaneous events. Lichenoid reactions, eczema, and vitiligo are the 3 most prevalent lesions observed in our population. There is a tendency for lichenoid reactions and eczema to occur with vitiligo.

Cited by 269 publications

References 26 publications

Cutaneous Eruptions in Patients Receiving Immune Checkpoint Blockade

Cutaneous Eruptions in Patients Receiving Immune Checkpoint Blockade

Bullous pemphigoid, an autoantibody-mediated disease, is a novel immune-related adverse event in patients treated with anti-programmed cell death 1 antibodies

Oral lichenoid reactions associated with anti‐PD‐1/PD‐L1 therapies: clinicopathological findings

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