Melanoma patient response to nivolumab treatment for metastatic lung lesions: Multi-OMICS analysis in Project HOPE

J Dermatol. 2017 Oct;44(10):1156-1159. doi: 10.1111/1346-8138.13879. Epub 2017 Apr 28.

Abstract

A 70-year-old woman was diagnosed with a malignant melanoma of the occipital skin which was resected; however, multiple lung metastases were detected. Nivolumab therapy was initiated and partial response was obtained. However, the patient was diagnosed with grade 2 interstitial pneumonitis. Prednisolone administration was initiated and the interstitial pneumonitis shadow disappeared. However, then a right rib metastasis was noticed and given radiation therapy. After progressive disease was obtained, the metastatic lesion was resected, and no relapse occurred until skeletal muscle metastasis was found. According to whole-exome sequencing and gene expression profiling, the rib and skeletal muscle metastatic lesions showed an upregulated expression of programmed death-ligand 1 mRNA and a high single-nucleotide variant (SNV) number. The current melanoma case is representative of a patient who responded to nivolumab therapy, and showed typical immunological markers for responders such as high PD-L1 expression and high SNV.

Keywords: anti-programmed death 1 blockade; immune-related pneumonitis; melanoma; mutation load; programmed death-ligand 1 expression.

MeSH terms

  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Bone Neoplasms / genetics
  • Bone Neoplasms / secondary
  • Bone Neoplasms / therapy*
  • Exome Sequencing
  • Female
  • Gene Expression Profiling / methods
  • Glucocorticoids / therapeutic use*
  • Humans
  • Lung / pathology
  • Lung Diseases, Interstitial / diagnostic imaging
  • Lung Diseases, Interstitial / drug therapy*
  • Lung Diseases, Interstitial / immunology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Melanoma, Cutaneous Malignant
  • Muscle Neoplasms / genetics
  • Muscle Neoplasms / secondary
  • Muscle, Skeletal / pathology
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / pathology
  • Nivolumab
  • Polymorphism, Single Nucleotide
  • Prednisolone / therapeutic use
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Ribs / diagnostic imaging
  • Ribs / pathology
  • Sequence Analysis, DNA
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Glucocorticoids
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • Prednisolone