Safety of immune checkpoint inhibitors in non-small-cell lung cancer patients with idiopathic interstitial pneumonia: a matched case–control study

Abstract

Purpose The immune checkpoint inhibitor nivolumab is commonly used for non-small-cell lung cancer treatment. Immune checkpoint inhibitors cause immune-related adverse events, including interstitial pneumonia. However, there are no studies on the risk factors for interstitial pneumonia exacerbation after immune checkpoint inhibitor administration in patients with a history of different types of interstitial pneumonia. Therefore, we aimed to investigate the risk factors for interstitial pneumonia exacerbation in patients with non-small-cell lung cancer and a history of interstitial pneumonia. We also aimed to explore differences in the risk of interstitial pneumonia exacerbation due to various types of interstitial pneumonia—idiopathic interstitial pneumonia, immune-related pneumonitis, and radiation pneumonitis. Methods Eleven patients with a history of interstitial pneumonia exacerbation following the administration of immune checkpoint inhibitor were included in the study. We performed 1:2 matching based on age and sex. Twenty-two patients whose interstitial pneumonia did not worsen after immune checkpoint inhibitor administration belonged to the control group. We calculated odds ratios for each factor in the patients and control subjects. Results The odds ratio of idiopathic interstitial pneumonia in the case group was 0.15 (95% confidence interval: 0.03–0.89) (p = 0.03). There were no significant differences in other factors, such as smoking history, pulmonary emphysema, and chronic obstructive pulmonary disease. Conclusion The administration of immune checkpoint inhibitors in non-small-cell lung cancer patients with a history of idiopathic interstitial pneumonia might be a viable treatment option and have clinical benefits.

Impact of treatment line on risks and benefits of immune checkpoint inhibitor in patients with advanced non-small cell lung cancer and interstitial lung disease: a systematic review and meta-analysis of cohort studies

“…In total, 319 records were screened and 300 articles were excluded based on their titles and abstracts. All investigators fully assessed the remaining 19 articles and agreed to include 17 eligible studies comprising 5,529 patients in the subsequent meta-analysis (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28).…”

“…Second, the pooled grade 3-5 ICIP rate was 12% (95% CI: 9-15%) (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)28). No statistically significant heterogeneity was obtained (I 2 =0.0%, P=0.64) and there was little variation among the studies (Figure 2B).…”

“…Of the six studies, only nivolumab was administered in five studies (12)(13)(14)23,26), and atezolizumab in one study (19). In the remaining nine studies, ICIs such as nivolumab, pembrolizumab, atezolizumab, and durvalumab were administered in various treatment lines (15)(16)(17)(20)(21)(22)24,27,28).…”

“…The pooled any-grade and grade 3-5 ICIP rates were obtained from 17 and 16 eligible studies, respectively (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). The pooled any-grade ICIP rate was 30% [95% confidence interval (CI): 24-36%] (12-28) and statistically significant heterogeneity was obtained through analysis (I 2 =53.7%, P=0.01) (Figure 2A).…”

“…Although the safety and efficacy have been evaluated in a few prospective observational studies with a small number of cases and multiple retrospective observational studies (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28), there is no consensus regarding the use of ICIs in NSCLC patients with pre-existing ILD. Thus, we performed a meta-analysis using the available reports to elucidate the risks and benefits of ICIs for advanced NSCLC patients with pre-existing ILD.…”