Second-line immunosuppressant administration for steroid-refractory immune-related adverse events in patients with lung cancer

Cancer Immunol Immunother. 2023 Nov;72(11):3765-3772. doi: 10.1007/s00262-023-03528-x. Epub 2023 Aug 28.

Abstract

Background: Evidence for use of second-line immunosuppressants for immune-related adverse events (irAEs) is inadequate. Therefore, a multicenter analysis should assess the efficacy of second-line immunosuppressants for severe irAEs associated with different malignant diseases.

Methods: This descriptive study aims to investigate the effects of second-line immunosuppressants on corticosteroid-refractory irAEs in patients with lung cancer. We analyzed the effects of second-line immunosuppressants on underlying lung cancer and associated adverse effects.

Results: Our study included 4589 patients who had received immune checkpoint inhibitor treatment, with 73 patients (1.6%) developing irAEs requiring second-line immunosuppressants. The most commonly observed irAE was pneumonitis (26 patients), followed by hepatobiliary disorders (15 patients) and enteritis (14 patients). We found a confirmed response rate of 42.3% for pneumonitis, which was lower than the response rates of 86.7% for hepatobiliary disorders and 92.9% for enteritis. The time from the start of corticosteroid therapy to the addition of a second-line immunosuppressant correlated significantly with the resolution of irAE to Grade 1 (correlation coefficients of r = 0.701, p < 0.005). The median progression-free survival and duration of response of underlying lung cancer from second-line immunosuppressant administration were 2.1 and 3.0 months, respectively. Of the patients with irAE, 27.4% developed infections and 5.5% might die due to infection.

Conclusion: Second-line immunosuppressant response was confirmed in 72.2% of irAEs in patients with lung cancer, with lower response rates observed in irAE pneumonitis compared to other irAEs.

Keywords: Corticosteroid-refractory; Immune-related adverse events; Lung cancer; Second-line immunosuppressants.

MeSH terms

  • Adrenal Cortex Hormones / adverse effects
  • Antineoplastic Agents, Immunological* / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Digestive System Diseases* / chemically induced
  • Enteritis* / chemically induced
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Lung Neoplasms* / pathology
  • Nivolumab / therapeutic use
  • Pneumonia* / chemically induced
  • Pneumonia* / etiology
  • Retrospective Studies
  • Steroids

Substances

  • Adrenal Cortex Hormones
  • Antineoplastic Agents, Immunological
  • Immunosuppressive Agents
  • Nivolumab
  • Steroids