Near complete response to Pembrolizumab in microsatellite-stable metastatic sebaceous carcinoma

J Immunother Cancer. 2018 Jun 19;6(1):58. doi: 10.1186/s40425-018-0357-3.

Abstract

Background: Sebaceous carcinoma is an aggressive adnexal skin tumor with a predilection for the eyelids and sebaceous glands of the head and neck.

Case presentation: A 73 year-old man presented with confusion and was found to have widely disseminated sebaceous carcinoma with metastases to brain, lungs, liver, bowel, lymph nodes, and bone. Following initial treatment of the brain metastases with surgery he received post-operative radiosurgery. He then began systemic immunotherapy with pembrolizumab. After 6 months, he developed a near complete response to therapy by irRECIST and RECIST v.1.1. The response was associated with circulating CD8+ T cells with central memory (CM) and effector memory (EM) phenotype and mature CD16 + CD57+ NK cells. During treatment the patient developed adrenal insufficiency requiring high-dose systemic corticosteroids and later adrenal replacement therapy. After 12-months of follow-up he showed imaging evidence of progression in liver, mediastinum, and abdominal lymph nodes. Given persistent, strong PD-L1 expression he resumed pembrolizumab therapy and showed radiographic evidence of an ongoing response to therapy.

Conclusions: This is the first report describing objective clinical and radiographic responses following immunotherapy for widely metastatic sebaceous carcinoma. The dramatic therapeutic response to pembrolizumab was associated with peripheral blood circulating memory T cells and mature Natural Killer cells after 6 months (24 weeks) of therapy. This report supports prospective clinical trials of anti-PD1 checkpoint blockade for metastatic sebaceous carcinoma.

Keywords: Anti-PD1; Immunotherapy; Pembrolizumab; Sebaceous carcinoma; Skin cancer5.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Humans
  • Male
  • Microsatellite Repeats
  • Positron Emission Tomography Computed Tomography
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Sebaceous Gland Neoplasms / diagnostic imaging
  • Sebaceous Gland Neoplasms / drug therapy*
  • Sebaceous Gland Neoplasms / genetics
  • Sebaceous Gland Neoplasms / pathology
  • Sequence Analysis, DNA
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • pembrolizumab