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

Sibaud, V.; Eid, Charbel Maroun; Belum, Viswanath Reddy; Combemale, P.; Barres, Béatrice; Lamant, Laurence; Mourey, Loïc; Gomez‐Roca, Carlos; Estilo, Cherry L.; Motzer, Robert J.; Vigarios, Émmanuelle; Lacouture, Mario E.

doi:10.1111/jdv.14284

Cited by 64 publications

(53 citation statements)

References 11 publications

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“…Patients developed extraoral and intraoral irAEs after a median of two infusions (range: 1 to 16) compared to a median of four infusions (range: 1–16) for patients who developed only oral irAEs. The median onset of oral irAE onset from PD‐1 inhibitor therapy initiation of 95 days (range: 7–284) was consistent with two prior reports ranging from 3 to 12 months (Shi et al, ; Sibaud et al, ).…”

Section: Discussionsupporting

confidence: 88%

“…A number of studies have reported the association of PD‐1 inhibitors with oral lichenoid reactions (Schaberg et al, ; Shi et al, ; Sibaud et al, ), SJS (Saw et al, ), toxic epidermal necrolysis (TEN) (Nayar et al, ), bullous pemphigoid (Jour et al, ), EM (Utsunomiya et al, ), and sicca syndrome (Cappelli et al, ; Teyssonneau, Cousin, & Italiano, ; Warner et al, ). Nevertheless, further characterization of oral lesions and management outcomes warrants study.…”

Section: Discussionmentioning

confidence: 99%

“…Sibaud et al . reported a cohort of 10 patients with oral lichenoid reactions secondary to PD‐1 inhibitor or PD‐L1 inhibitor therapy including nivolumab ( n = 5), pembrolizumab ( n = 2), and atezolizumab ( n = 3) (Sibaud et al, ). The lesions were described as white reticulated striations on the buccal mucosa, tongue, and palate, with erythema and/or ulceration.…”

Section: Discussionmentioning

confidence: 99%

“…PD‐1 inhibitor therapy was temporarily discontinued (with or without ongoing steroid treatment) because of severe oral ulcerations ( n = 2) and discontinued indefinitely due to severe oral EM‐like lesions ( n = 1) and acute GVHD reactivation ( n = 1), suggesting that oral irAEs alone can be severe enough to necessitate PD‐1 inhibitor therapy modification. In contrast, Sibaud et al reported that oral lesions were managed with some form of topical corticosteroid therapy, although specifics were not provided, and patients did not require discontinuation of immunotherapy. Shi et al reported four out of twenty patients (20%) required temporary discontinuation of PD‐1 inhibitor nivolumab due to cutaneous irAEs, but all patients were able to resume therapy with some form of topical or systemic corticosteroid.…”

Section: Discussionmentioning

confidence: 99%

“…Although the use of PD‐1 inhibitors in oncology continues to grow at a rapid rate, there have been scarce descriptions of oral irAEs (Tang et al, ). Thus far, oral irAEs have been shown to include lichenoid reactions, vesiculobullous disorders, erythema multiforme (EM), and Steven–Johnson syndrome (SJS) (Goldinger et al, ; Nayar, Briscoe, & Fernandez Penas, ; Salati et al, ; Saw, Lee, & Ng, ; Schaberg et al, ; Shi et al, ; Sibaud et al, ; Utsunomiya et al, ). Moreover, the association between oral irAEs and the discontinuation of PD‐1 inhibitor therapy and their management strategies and outcomes have not been well‐documented.…”

Section: Introductionmentioning

confidence: 99%

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Oral immune‐related adverse events associated with PD‐1 inhibitor therapy: A case series

et al. 2020

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Objective The aim of this study was to characterize clinical and histopathological features, and management outcomes of patients with oral immune‐related adverse events (irAEs) secondary to programmed cell death‐1 (PD‐1) inhibitors. Methods This was a case series of cancer patients receiving PD‐1 inhibitor therapy who were referred to oral medicine for the development of oral irAEs. Demographic, clinical, and histopathological data were collected from electronic medical records. Results There were 13 patients (7 males) with a median age of 68 years (range: 39–82) who were treated with nivolumab (n = 7) or pembrolizumab (n = 6). Oral irAEs included lichenoid lesions (n = 10), erythema multiforme (EM) (n = 2), and acute graft‐versus‐host disease reactivation (n = 1), with or without ulcerations (n = 8). Four patients (31%) presented with only oral irAEs. Oral biopsies showed lichenoid mucositis (n = 4). Management with topical and systemic steroids led to complete symptomatic response in most patients (n = 12). PD‐1 inhibitor therapy was temporarily discontinued (n = 3) and discontinued indefinitely (n = 2) due to severe oral irAEs. Conclusion Patients receiving PD‐1 inhibitors may develop oral irAEs characterized by lichenoid lesions, ulcers, or EM. Topical and systemic steroids appear to be effective in managing oral lesions although the severity of irAEs may necessitate PD‐1 inhibitor therapy dose modification.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Oral immune‐related adverse events associated with PD‐1 inhibitor therapy: A case series

et al. 2020

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Oral side effects of immune checkpoint inhibitor therapy (ICIT): An analysis of 4683 patients receiving ICIT for malignancies at Massachusetts General Hospital, Brigham & Women's Hospital, and the Dana‐Farber Cancer Institute, 2011 to 2019

Wen

Sonis

et al. 2021

Cancer

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Background Immune checkpoint inhibitors (ICIs) are increasingly accepted as a treatment option for several cancers. Although various systemic immune‐related adverse events (irAEs) have been characterized, the effect of ICIs on the oral cavity and contiguous structures is still poorly understood. Methods Electronic medical records of 4683 patients in the Mass General Brigham Registered Patient Data Registry who received ICI therapy (ICIT) between December 2011 and September 2019 were reviewed. Reports of oral conditions were categorized into oral mucosal disorders, xerostomia, and dysgeusia. After applying exclusion criteria, demographic characteristics and clinical features were summarized for the patients who had oral irAEs. Results In total, 317 patients developed oral conditions that were associated with ICIT (incidence, 6.8%; 317 of 4683 patients). These conditions included xerostomia (68.5%), oral mucosal disorders (33.4%), and dysgeusia (24.0%). In patients with oral irAEs, respiratory cancer (28.4%) was the most common primary cancer, followed by melanoma (26.2%), and head and neck cancer (14.8%). Oral mucosal disorders developed after the initiation of ICIT between 2 and 851 days (between 1 and 1332 days in patients with xerostomia and between 1 and 1455 days in patients with dysgeusia). Of all oral irAEs, 50.9% developed within 3 months, and 85.5% developed within 12 months. Conclusions Oral side effects appear to be more common among patients who receive ICIT than has been previously reported. Concomitant cytotoxic regimens may exacerbate the risk of oral adverse events, perhaps representing the sum of the effects of different, but simultaneous or sequential, pathogenic mechanisms. Additional studies are warranted to better characterize oral irAEs and their biologic basis.

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Pembrolizumab‐induced acquired perforating dermatosis

Gu,

de Silva,

Henderson

et al. 2024

JEADV Clinical Practice

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Immune checkpoint inhibitors such as the programmed cell death‐1 (PD‐1) inhibitors, pembrolizumab and nivolumab, are frontline treatments for several types of solid‐organ malignancies. However, cutaneous adverse effects with PD‐1 inhibitor therapy are common and include lichenoid reactions, eczema, vitiligo and bullous dermatoses. Perforating dermatosis is a rare condition characterised by the extrusion of degenerate materials from the upper dermis through the epidermis and has rarely been reported in association with PD‐1 inhibitor therapy. Herein, we report the first case to our knowledge of acquired perforating dermatosis following treatment with pembrolizumab.

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

Cited by 64 publications

References 11 publications

Oral immune‐related adverse events associated with PD‐1 inhibitor therapy: A case series

Oral immune‐related adverse events associated with PD‐1 inhibitor therapy: A case series

Oral side effects of immune checkpoint inhibitor therapy (ICIT): An analysis of 4683 patients receiving ICIT for malignancies at Massachusetts General Hospital, Brigham & Women's Hospital, and the Dana‐Farber Cancer Institute, 2011 to 2019

Pembrolizumab‐induced acquired perforating dermatosis

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