CSCC Lesions Found in Few Patients Treated With PD-1/PD-L1 Checkpoint Inhibition

An analysis of patients who presented to MD Anderson Cancer Center’s dermatology clinic following treatment with anti—PD-1/PD-L1 treatment suggests a potential association between the development of cutaneous squamous cell carcinoma (CSCC) lesions and PD-1/PD-L1 checkpoint inhibition. Findings from the analysis were presented in a poster presentation at the 33^rdSociety for Immunotherapy of Cancer Annual Meeting.¹

“While this link has yet to be solidified, we are actively investigating factors that may contribute to the development of these lesions in the setting of immune checkpoint inhibitor therapy,” the study authors, led by Amanda Herrmann, an immunology student of the MD Anderson Cancer Center—UTHealth Graduate School of Biomedical Sciences, wrote in their poster.

Cutaneous adverse events have been seen in about 40% of patients with melanoma who have been treated with PD-1 inhibition²; however, few cases of new CSCC lesions have previously been noted.

Ten patients who were treated at MD Anderson Cancer Center were included in the analysis. Each patient was undergoing or had completed treatment with PD-1/PD-L1 checkpoint inhibition for a nonsquamous cell cancer. Seven of these patients presented to the dermatology clinic within a span of 5 years when skin lesions were discovered during the course of their treatment. An additional 3 patients were discovered in a retrospective chart review.

Of the 10 patients, 8 were male and 2 were female. The ages ranged from 51 to 81. The underlying cancers were malignant melanoma, pancreatic, and Merkel cell carcinoma. Six patients had received additional prior therapy, mostly chemotherapy and/or radiation, and 4 had previous incidences of well-differentiated CSCC, but had not had a reported recurrence.

Half of the patients were receiving treatment with pembrolizumab (Keytruda). Two of the patients were receiving PD-1/PD-L1 inhibition as part of a combination regimen, including BRAF inhibition with vemurafenib (Zelboraf), and 1 patient also received added cobimetinib (Cotellic).

CSCC, including a total of 27 lesions, developed in patients after a median of 4 months (range, 3-16) following the start of treatment. Most (74%) developed during the course of treatment and the majority of lesions were located on the patient’s extremity.

Biopsies were conducted to confirm the diagnosis of CSCC, and all lesions were well differentiated with full thickness keratinocyte atypia. The biopsies were also tested with H&E staining and immunohistochemical antibody analysis for CD3, CD8, PD-1, and PD-L1.

PD-L1 expression was present in 63% and was noted in a median of 5% (range, 1%-13%) of the peripheral immune cell infiltrate. Normal proportions of CD3:CD8 T lymphocytes were noted at the periphery of the tumor.

The study authors found the development of the lesions “perplexing” as anti—PD-1/PD-L1 therapy has typically been used to successfully treat skin cancers.

Treatment was postponed in 1 patient following the development of the CSCC lesions and resolved within a few months, showing the low-grade nature of the lesions.

Regarding next steps, the authors wrote that they “plan to compare CSCC samples resulting from various etiologies, including BRAF inhibitor—induced CSCC and ultraviolet light-induced CSCC, to determine if there are unique characteristics in the CSCC from our immune checkpoint inhibitor–associated tumor cohort of patients.”

“These results will be important to clinicians moving forward, as the use of this class of therapeutics rapidly increases, and may soon include the treatment of advanced CSCC,” they added.

References:

1. Herrmann A, Nagarajan P, Subbiah V, et al. Development of cutaneous squamous cell carcinoma in patients receiving anti-PD-1/PD-L1 immune checkpoint blockade. Presented at: 33^rdSITC Annual Meeting; November 7-11, 2018; Washington, DC. Abstract P539.
2. Villadolid J, Amin A. Immune checkpoint inhibitors in clinical practice: update on management of immune-related toxicities.Transl Lung Cancer Res.2015;4(5):560-575. doi: 10.3978/j.issn.2218-6751.2015.06.06.