Progressive hypoventilation due to mixed CD8+ and CD4+ lymphocytic polymyositis following tremelimumab - durvalumab treatment

J Immunother Cancer. 2017 Jul 18;5(1):54. doi: 10.1186/s40425-017-0258-x.

Abstract

Background: The combination of CTLA-4 and PD-L1 inhibitors has a manageable adverse effect profile, although rare immune-related adverse events (irAE) can occur.

Case presentation: We describe an autoimmune polymyositis following a partial response to combination tremelimumab and durvalumab for the treatment of recurrent lung adenocarcinoma. Radiography revealed significant reduction in all metastases; however, the patient developed progressive neuromuscular hypoventilation due to lymphocytic destruction of the diaphragmatic musculature. Serologic testing revealed a low level of de novo circulating antibodies against striated muscle fiber. Immunohistochemistry revealed type II muscle fiber atrophy with a mixed CD8+ and CD4+ lymphocyte infiltrate, indicative of inflammatory myopathy.

Conclusions: This case supports the hypothesis that muscle tissue is a target for lymphocytic infiltration in immune checkpoint inhibitor-associated polymyositis. Further insights into the autoimmune mechanism of PM will hopefully contribute to the prevention and treatment of this phenomenon.

Keywords: Cytotoxic T-lymphocyte-associated-protein 4; Immune checkpoint inhibitor; Immune-related adverse event; MEDI4736; Myasthenia gravis; Non-small cell lung cancer; Programmed death protein 1; Programmed death-ligand 1; Striated muscle antibody.

Publication types

  • Case Reports

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Fatal Outcome
  • Female
  • Humans
  • Hypoventilation / chemically induced*
  • Leukemic Infiltration / chemically induced
  • Leukemic Infiltration / immunology
  • Lung Neoplasms / drug therapy
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Polymyositis / chemically induced*
  • Respiratory Muscles / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • durvalumab
  • tremelimumab