Rechallenge with Immune Checkpoint Inhibitors in Patients with Lung Cancer Associated with More Severe Interstitial Lung Disease

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Immune checkpoint inhibitors (ICIs) block checkpoint molecules that work to negatively regulate immunity.1 Blocking the checkpoint molecules activates the host’s immune system.1 PD-1, PD ligand 1, and anti–CTLA-4 are immune checkpoint molecules inhibited by ICIs during lung cancer treatment with ICIs.1 Use of ICIs in lung cancer, both alone and in combination with other antitumor therapies, has improved clinical outcomes.1 By activating the host’s immune system, ICI use can lead to immune-related adverse events (irAEs) that affect various organs in the body.1 Most of these irAEs can be managed successfully, but ICI-related interstitial lung disease has the potential to lead to severe disease and mortality.1 Interstitial lung disease related to ICI treatment has a low incidence rate of 1% to 5% in most cancers, but in lung cancer the incidence rate has been reported to be as high as 14.5%.1

A multicenter retrospective study was conducted recently on the safety and efficacy of immunotherapy rechallenge after the first episode of ICI-related interstitial lung disease. In this study, 32 participants were enrolled who had been either initially treated with anti–PD-1 monotherapy or combined with anti–CTLA-4 therapy. Anti–PD-1 therapy was given to 84% of the patients while combined therapy was given to 15.6%. All patients experienced ICI-related interstitial lung disease, with 25% experiencing grade 1, 56.2% experiencing grade 2, and 18.8% experiencing grade 3 interstitial lung disease due to immunotherapy. Rechallenge with anti–PD-1 monotherapy was given to 90.6% of these patients. Interstitial lung disease recurrence occurred in 13 of the rechallenged patients. Median time to recurrence was 0.9 months for the rechallenged patients compared with 3.0 months for first occurrence. Evaluation of symptoms revealed the second episode was more severe, with 38% having grade 3 or higher on second occurrence versus 18.8% on first occurrence. Similar radiological patterns were found in 53.8% of patients with more severe radiological features found on second occurrence. One death was attributed to ICI interstitial lung disease with rechallenge. There was no association of ICI interstitial lung disease recurrence with steroid use during the rechallenge. The objective response rate under ICI rechallenge was 18.8% and disease stabilization was 34.4%. Analysis found no statistical difference in patients who experienced recurrence of ICI interstitial lung disease and those patients who did not experience a recurrence. At 3 months after rechallenging, 15 patients had progressive disease, 55.6% were in the recurrence group, and 43.6% were in the no recurrence group.


Joseph C, Mazieres J, Delaunay M, et al. Safety and efficacy of immunotherapy rechallenge following a previous immune-induced interstitial lung disease. Ann Oncol. 2022;33:s118-s119.


  1. Okada N, Matsuoka R, Sakurada T, et al. Risk factors of immune checkpoint inhibitor-related interstitial lung disease in patients with lung cancer: a single-institution retrospective study. Sci Rep. 2020;10:13773.

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