*8.2. Applicability Among Patients with a History of Interstitial Pneumonia or Autoimmune Disease*

Managing irAE is of great importance with the use of ICIs. Characteristic adverse events that are less common but not experienced with cytotoxic anticancer drugs or molecular-targeted agents have become evident. Regarding disease management after manifestation, close cooperation among medical care departments is important as the AEs seem to be caused by immune activity in all organs.

Regarding the risk factors for irAE, ICIs activate the autoimmune system and induce antitumor effects. In patients with a history of autoimmune disease or interstitial pneumonitis, exacerbation of these underlying diseases or an increased incidence of irAE are worrisome and thus, cautious administration is recommended.

Furthermore, a higher incidence of smoking, and numerous cases with complications of smoking-related interstitial pneumonia have been reported. The use of ICIs among patients with interstitial pneumonia or autoimmune diseases is often excluded in clinical trials, and a few retrospective data have been reported.

Fujimoto et al. reported that 2 of 18 patients with mild-to-moderate idiopathic interstitial pneumonia had grade-II pneumonitis and that pneumonitis was alleviated in 6 patients with moderate pneumonitis upon nivolumab treatment [53]. The incidence of pneumonitis with previous ICIs did not significantly increase as the all-grade incidence of pneumonitis in ICIs ranged from 5% to 10%. On the contrary, Kanai et al. reported that the incidence of pneumonitis upon nivolumab treatment was significantly higher in the group with a history of interstitial pneumonia (31% vs. 12%), and 62% vs. 45% for grade-III or higher was associated with higher risks in the group with a history of interstitial pneumonia [54]. No deaths due to pneumonitis were recorded in these reports.

Leonardi et al. reported that treatment with ICIs alone among patients with autoimmune diseases resulted in disease exacerbation in 23% of patients, of which 32% required treatment with steroids [55]. Moreover, 38% developed some form of irAE, of which 26% were grade-III or higher [55]. Overall, 55% of patients experienced exacerbations of irAE, autoimmune disease, or both, and the incidence of irAE was similar to that in patients without autoimmune disease [55].

These reports on patients with a history of interstitial pneumonia or autoimmune disease provide retrospective data; however, it is considered necessary to exclude patients who judge the use of ICIs to be inappropriate based on their condition.

Studies wherein patients with interstitial pneumonia or autoimmune disease were administered ICIs have not provided adequate data on their safety and efficacy, and caution should be exercised with their use. In particular, the benefit for patients with high PD-L1 expression levels seems to be non-negligible, and individualized correspondence is required considering the balance with risk.
