Dramatic response to nivolumab in xeroderma pigmentosum skin tumor

Abstract

We report the case of a 6-year-old female with xeroderma pigmentosum (XP) who developed a nonoperable scalp tumor, treated with anti-programmed cell death protein 1 (anti-PD-1) therapy (nivolumab). She presented with a sarcomatoid carcinoma of the scalp with bone lysis as well as vascular and meningeal contact. Nivolumab was initiated because it has emerged as a promising immunotherapy. We observed a dramatic tumor response with excellent tolerance. However, while on nivolumab therapy she developed two large skin melanomas and several squamous cell carcinomas, which have been resected. These results demonstrate that cancer immunotherapy in patients with XP can be impressive but complex and warrants further investigation.

Immunotherapy in Xeroderma Pigmentosum: a case of advanced cutaneous squamous cell carcinoma treated with cemiplimab and a literature review

“…Immune checkpoint inhibitors (ICIs) interfere with the escape mechanisms used by tumoral cells to evade immunosurveillance. Treatment of XP-associated advanced skin tumours with ICIs has been previously described, and, in order to shed light on outcome of their administration, we gathered all the cases reported in the available literature on Pubmed so far (Table 1) [6][7][8][9][10][11][12]. To the best of our knowledge, our case is the first in which cemiplimab was used.…”

“…The immunotherapy was also effective in two cases where traditional chemotherapy did not work, specifically nivolumab against a sarcomatoid carcinoma of the scalp [ 7 ] and pembrolizumab for a cutaneous angiosarcoma of the face [ 12 ].…”

Immune Checkpoint Blockade in Advanced Cutaneous Squamous Cell Carcinoma: What Do We Currently Know in 2020?

“…The case reports described above have demonstrated that ICB may be a suitable systemic therapy option for XP patients affected by advanced, unresectable cSCC [75,78]. In addition, other case reports which did not clearly distinguish between cSCC and other skin tumors and, therefore, were not included in the list above, underline the efficacy of ICB against melanoma and NMSC [118][119][120][121].…”

DNA repair defects and implications for immunotherapy

“…These patients harbor germline defects in one of eight genes in the NER pathway and are highly susceptible to the development of skin and mucous membrane cancers (60). Due to the extreme rarity of this syndrome, documentation of clinical activity of CPIs is limited to case reports; however, dramatic and durable responses have been reported in melanomatous and nonmelanomatous XP-associated skin cancers (61)(62)(63)(64)(65). Somatic alterations in the NER pathway and particularly in the ERCC genes are commonly observed and may have implications for immunotherapy.…”