Pembrolizumab for Treatment of a Patient With Multiple Cutaneous Squamous Cell Carcinomas and Recessive Dystrophic Epidermolysis Bullosa

Piccerillo, Alfredo; Hachem, Maya El; Vito, Rita De; Luca, Emilia; Peris, Ketty

doi:10.1001/jamadermatol.2020.0304

Cited by 16 publications

(11 citation statements)

References 6 publications

(14 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cemiplimab, a PD-1 inhibitor approved by the Food and Drug Administration and European Medicines Agency for the treatment of advanced cutaneous SCC, was administered to one of our cohort who had partial tumour regression. This, and other PD-1 inhibitors such as nivolumab and pembrolizumab, both approved for the management of advanced head and neck SCC, may have a role in EB SCC palliation (26,(28)(29)(30)(31). Following in vitro work in EB SCC cell lines and an in vivo mouse model (32), a clinical trial of the polo-like kinase inhibitor rigosertib is currently underway (ClinicalTrials.gov: NCT01807546).…”

Section: Squamous Cell Carcinoma Treatmentmentioning

confidence: 99%

Cutaneous Squamous Cell Carcinoma in Epidermolysis Bullosa: a 28-year Retrospective Study

Robertson¹,

Orrin²,

Lakhan³

et al. 2021

Acta Derm Venereol

View full text Add to dashboard Cite

This series is the largest reported to date and highlights that individuals with different forms of epidermolysis bullosa are at risk of developing squamous cell carcinomas of the skin. Patients often develop multiple primary tumours that tend to behave aggressively despite wide local excision and have poor response to conventional chemotherapy. The prognosis in severe recessive dystrophic epidermolysis bullosa is worse than previously reported, with median survival from diagnosis of first squamous cell carcinoma of only 2.4 years.Epidermolysis bullosa (EB), notably severe recessive dystrophic EB (RDEB-S), is associated with increased risk of aggressive mucocutaneous squamous cell carcinomas, the major cause of mortality in early adulthood. This observational, retrospective case review describes a series of EB patients with cutaneous squamous cell carcinomas over a 28-year period. Forty-four EB patients with squamous cell carcinomas were identified with a total of 221 primary tumours. They comprised: 31 (70%) with RDEB-S, 4 (9%) with other RDEB subtypes, 5 (11.4%) with dominant dystrophic EB, 3 (6.8%) with intermediate junctional EB and 1 (2.3%) with Kindler EB. Squamous cell carcinomas occurred earlier in RDEB-S (median age 29.5 years; age range 13-52 years) than other groups collectively (median age 47.1 years; age range 30-89 years) and most had multiple tumours (mean 5.8; range 1-44). Squamous cell carcinoma-associated mortality was high in RDEB-S (64.5%), with median survival after first squamous cell carcinoma of 2.4 years (range 0.5-12.6 years), significantly lower than previous reports, highlighting the need for early surveillance and better treatments.

show abstract

Section: Squamous Cell Carcinoma Treatmentmentioning

confidence: 99%

Cutaneous Squamous Cell Carcinoma in Epidermolysis Bullosa: a 28-year Retrospective Study

Robertson¹,

Orrin²,

Lakhan³

et al. 2021

Acta Derm Venereol

View full text Add to dashboard Cite

show abstract

“…In patients with severe forms of RDEB, it is likely that > 50% of them will develop SCC by the age of 40 years and that the majority will not survive for > 5 years after the SCC first appears [156]. Treatment options are limited: apart from surgery, there are anecdotal reports on the use of epidermal growth factor receptor (EGFR) antagonists and programmed cell death protein 1 (PD-1) receptor antibodies, but response rates are variable (usually poor) and clinical trial data are lacking [157][158][159][160][161][162][163][164]. In contrast, in vitro studies in RDEB SCC have identified upregulation of Polo-kinase 1 (PLK1), and demonstrated that several PLK1 inhibitors, including rigosertib, can specifically induce cell cycle arrest and apoptosis of RDEB SCC keratinocytes as well as reduce the tumor volume of in vivo tumor xenografts while displaying minimal interference with the non-SCC tissue [165,166].…”

Section: Squamous Cell Carcinoma Therapymentioning

confidence: 99%

Investigational Treatments for Epidermolysis Bullosa

et al. 2021

View full text Add to dashboard Cite

Epidermolysis bullosa (EB) is a heterogeneous group of rare inherited blistering skin disorders characterized by skin fragility following minor trauma, usually present since birth. EB can be categorized into four classical subtypes, EB simplex, junctional EB, dystrophic EB and Kindler EB, distinguished on clinical features, plane of blister formation in the skin, and molecular pathology. Treatment for EB is mostly supportive, focusing on wound care and patient symptoms such as itch or pain. However, therapeutic advances have also been made in targeting the primary genetic abnormalities as well as the secondary inflammatory footprint of EB. Pre-clinical or clinical testing of gene therapies (gene replacement, gene editing, RNA-based therapy, natural gene therapy), cell-based therapies (fibroblasts, bone marrow transplantation, mesenchymal stromal cells, induced pluripotential stem cells), recombinant protein therapies, and small molecule and drug repurposing approaches, have generated new hope for better patient care. In this article, we review advances in translational research that are impacting on the quality of life for people living with different forms of EB and which offer hope for improved clinical management.

show abstract

“…[ 72 ] While the latter have become a standard treatment for advanced non‐EB SCC, administration in EB patients is only anecdotally reported. [ 73–75 ] Thus, their therapeutic and immunomodulatory impact on EB hitherto remains largely unknown, including potentially disadvantageous effects on barrier integrity, local and systemic inflammatory state, microbial burden and susceptibility to skin infections. In addition, common autoimmune skin (eg rash and pruritus) and gastrointestinal (eg diarrhoea) toxicities (may be challenging for critical stage IV tumor patients with dystrophy and severe cutaneous involvement, which is characteristic of RDEB phenotypes.…”

Section: Targeted Anti‐tumor Therapy In Ebmentioning

confidence: 99%

Translational perspectives to treat Epidermolysis bullosa—Where do we stand?

Prodinger

Bauer

Laimer

2020

Experimental Dermatology

View full text Add to dashboard Cite

Epidermolysis bullosa (EB) comprises a group of rare, genetically determined skin fragility disorders characterized by (muco-) cutaneous blistering following mild mechanical trauma. The most recent classification guidelines published in February 2020 define EB as the prototypic genetic disorder of skin fragility. Other skin fragility disorders, including peeling skin disorders, erosive disorders, hyperkeratotic disorders and connective tissue disorders with skin fragility, are now classified as a separate category, that is so-called

show abstract

Pembrolizumab for Treatment of a Patient With Multiple Cutaneous Squamous Cell Carcinomas and Recessive Dystrophic Epidermolysis Bullosa

Cited by 16 publications

References 6 publications

Cutaneous Squamous Cell Carcinoma in Epidermolysis Bullosa: a 28-year Retrospective Study

Cutaneous Squamous Cell Carcinoma in Epidermolysis Bullosa: a 28-year Retrospective Study

Investigational Treatments for Epidermolysis Bullosa

Translational perspectives to treat Epidermolysis bullosa—Where do we stand?

Contact Info

Product

Resources

About