Treatment of mycophenolate-resistant immune-related organizing pneumonia with infliximab

J Immunother Cancer. 2018 Sep 3;6(1):85. doi: 10.1186/s40425-018-0400-4.

Abstract

Background: The development of pulmonary immune-related adverse events (irAEs) in patients undergoing PD-(L)1 targeted checkpoint inhibitors are rare, but may be life-threatening. While many published articles and guidelines are focusing on the presentation and upfront treatment of pulmonary irAEs, the strategy in patients with late-onset pneumonia that are resistant to commonly used immunosuppressive drugs remains unclear.

Case presentation: Here, we report the successful treatment of a mycophenolate-resistant organizing pneumonia (OP) with infliximab in a patient with metastatic melanoma after PD-1 blockade. The patient received two years of PD-1 targeted immunotherapy when he developed multiple nodular lung lesions mimicking a metastatic progression. However, wedge resection of these lesions showed defined areas of OP, which responded well to corticosteroids. Upon tapering, new foci of OP developed which were resistant to high-dose steroids and mycophenolate treatment. The TNFα antagonist infliximab led to a rapid and durable regression of the inflammatory lesions.

Conclusion: This case describes a not well-studied situation, in which a mycophenolate-resistant PD-1 blocker-associated pneumonitis was successfully treated with a TNFα neutralizing antibody. The outcome of this case suggests that infliximab might be the preferable option compared to classical immunosuppressants in the case of steroid-resistant/-dependent late onset pulmonary irAEs.

Keywords: Cancer immunotherapy; Immune checkpoint inhibitor; Immune-related adverse event; Lung; Pneumonitis.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents, Immunological / adverse effects*
  • CTLA-4 Antigen / antagonists & inhibitors
  • Drug Resistance, Neoplasm
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Infliximab / therapeutic use*
  • Ipilimumab / therapeutic use
  • Male
  • Melanoma / drug therapy
  • Mycophenolic Acid / therapeutic use
  • Pneumonia / chemically induced*
  • Pneumonia / drug therapy*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Antineoplastic Agents, Immunological
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immunosuppressive Agents
  • Ipilimumab
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • pembrolizumab
  • Mycophenolic Acid