Severe nivolumab-induced pneumonitis preceding durable clinical remission in a patient with refractory, metastatic lung squamous cell cancer: a case report

Hong Li, Weijie Ma, Ken Y Yoneda, Elizabeth H Moore, Yanhong Zhang, Lee Li-Qun Pu, Garrett M. Frampton, Michael Molmen, Philip J. Stephens, Tianhong Li

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Background: Programmed cell death 1 (PD-1) and its ligand 1 (PD-L1) inhibitors have quickly become standard of care for patients with advanced non-small cell lung cancer and increasing numbers of other cancer types. In this report, we discuss the clinical history, pathological evaluation, and genomic findings in a patient with metastatic lung squamous cell cancer (SCC) who developed severe nivolumab-induced pneumonitis preceding durable clinical remission after three doses of nivolumab. Case presentation: A patient with chemotherapy-refractory, metastatic lung SCC developed symptomatic pneumonitis by week 4 after nivolumab treatment, concurrently with onset of a potent antitumor response. Despite discontinuation of nivolumab after three doses and the use of high dose oral corticosteroids for grade 3 pneumonitis, continued tumor response to a complete remission by 3 months was evident by radiographic assessment. At the time of this submission, the patient has remained in clinical remission for 14 months. High PD-L1 expression by immunohistochemistry staining was seen in intra-alveolar macrophages and viable tumor cells in the pneumonitis and recurrent tumor specimens, respectively. Tumor genomic profiling by FoundationOne targeted exome sequencing revealed a very high tumor mutation burden (TMB) corresponding to 95-96 percentile in lung SCC, i.e., 87.4-91.0 and 82.9 mut/Mb, respectively, in pre- and post-nivolumab tumor specimens. Except for one, the 13 functional genomic alterations remained the same in the diagnostic, recurrent, and post-treatment, relapsed tumor specimens, suggesting that nivolumab reset the patient’s immune system against one or more preexisting tumor-associated antigens (TAAs). One potential TAA candidate is telomerase reverse transcriptase (TERT) in which an oncogenic promoter -146C>T mutation was detected. Human leukocyte antigen (HLA) typing revealed HLA-A*0201 homozygosity, which is the prevalent HLA class I allele that has been used to develop universal cancer vaccine targeting TERT-derived peptides. Conclusions: Nivolumab could quickly reset and sustain host immunity against preexisting TAA(s) in this chemotherapy-refractory lung SCC patient. Further mechanistic studies are needed to characterize the effective immune cells and define the HLA-restricted TAA(s) and the specific T cell receptor clones responsible for the potent antitumor effect, with the aim of developing precision immunotherapy with improved effectiveness and safety.

Original languageEnglish (US)
Article number64
JournalJournal of Hematology and Oncology
Volume10
Issue number1
DOIs
StatePublished - Feb 28 2017

Keywords

  • Cancer immunotherapy
  • Complete remission
  • HLA
  • Immune-related adverse event
  • Nivolumab
  • PD-1 inhibitor
  • Pneumonitis
  • Targeted exome sequencing
  • Tumor genomic profiling
  • Tumor mutation burden

ASJC Scopus subject areas

  • Hematology
  • Molecular Biology
  • Oncology
  • Cancer Research

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