Vitiligo-like depigmentation after pembrolizumab treatment in patients with non-small cell lung cancer: a case report

Abstract

Immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) pathway have significantly improved outcomes for patients with a variety of malignancies, including non-small cell lung cancer (NSCLC). In contrast, the incidence of immune-related cutaneous adverse events such as vitiligo have been on the rise because of the increasing use of ICIs. Vitiligo-like depigmentation has been reported in only 2.0% to 8.3% of patients with melanoma and is considered a favorable prognostic factor. However, it has been rarely reported in patients with non-melanoma malignancies. We describe a case of vitiligo-like skin depigmentation after pembrolizumab use in a patient with stage IV NSCLC. Multiple ill-defined painless and non-pruritic depigmented patches appeared on the patient's hands, scrotum, and lower lip after five months of pembrolizumab. We continued treatment with pembrolizumab 2 mg/kg for 14 months with close monitoring of vitiligo lesions until the progression of brain metastasis, but the vitiligo-like depigmentation did not improve by the combined excimer laser and topical corticosteroid therapy. Clinicians should be aware that immune-related cutaneous adverse events such as vitiligo-like depigmentation are not limited to cases of melanoma but arise as a direct result of anti-PD-1 therapy.

Case Report: Immune checkpoint inhibitor-related vitiligo-like depigmentation in non-melanoma advanced cancer: A report of three cases and a pooled analysis of individual patient data

“…5 2 % ) , a c u t e m y e l o i d l e u k e m i a ( 1 / 2 1 , 4 . 7 6 % ) , cholangiocarcinoma (1/21, 4.76%), urothelial carcinoma (1/21, 4.76%), oral squamous cell carcinoma (1/21, 4.76%), esophageal squamous cell carcinoma (1/21, 4.76%), and gastric adenocarcinoma (1/21, 4.76%) (2,4,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). The severity of vitiligo-like depigmentation after the use of immunotherapy was not related to sex, age, cancer type, previous autoimmune diseases, or medication(P>0.05, Table 2).…”

Method for high‐plex analysis of immune cells in human skin using the GeoMx system

“…The role of PD‐1 has been explored both in mouse models and a potential therapeutic target in humans 23,24 . It has been noted that patients undergoing cancer therapy blocking PD‐1 signalling, a type of checkpoint inhibitor, can develop therapy‐induced vitiligo 25 …”

“…Such contamination may show falsely elevated protein of interest levels. Ultimately our method aided in the identification of several differentially expressed proteins between the different areas in vitiligo and healthy skin, including clinically relevant proteins S100B, a melanocyte intracellular protein suggested as a marker following vitiligo patients, 22 and PD‐1 in which inhibition can lead to development of vitiligo in cancer patients undergoing checkpoint immune therapy 25 . Taken the large number of proteins that can be simultaneously measured by GeoMx, this method has the potential to provide tissue‐wide multiplex analysis of small tissue samples.…”

The time window for the reversal of depigmentation from aggravation to recovery in a non-small-cell lung cancer patient with pre-existing vitiligo using anti-programmed cell death-1 therapy: A case report

“…One case of nivolumab-induced vitiligo was successfully treated with narrowband ultraviolet light therapy ( 26 ). But in another study, pembrolizumab-associated vitiligo-like depigmentation was not improved by the combination of the excimer laser and topical corticosteroid therapy ( 27 ). In our study, the patient did not receive any hormones or other treatment for vitiligo since her quality of life was not additionally affected.…”