Analysis of baseline interstitial lung abnormality on the risk of checkpoint inhibitor-related pneumonitis and survival in advanced non-small cell lung cancer patients treated with first-line PD-1/PD-L1 inhibitors.

Background: Chest computed tomography (CT) can be used to identify interstitial lung abnormality (ILA), which is known to lead to an increased risk of post-operative complications, and is related to a worse prognosis in early-stage lung cancer. However, research on the role of ILA in advanced non-small cell lung cancer (NSCLC) patients receiving immunotherapy is limited. This study sought to investigate the effect of pre-existing ILA and pulmonary function test (PFT) results on the occurrence of checkpoint inhibitor-related pneumonitis (CIP) and survival in advanced NSCLC patients after programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) inhibitor therapy.

Methods: We retrospectively divided the patients with advanced NSCLC into two groups: the with ILA group, and the without ILA group. We also divided the patients into two groups based on whether they developed CIP during treatment. After first-line immunotherapy, we followed up with all patients and recorded their progression-free survival (PFS) and overall survival (OS). Two respiratory specialists recorded the cases of CIP and the existence of ILA on chest CT, and assessed the consistency of ILA. A logistic regression analysis was performed to explore the independent risk factors for CIP, and a Cox regression analysis was performed to investigate the factors influencing PFS and OS.

Results: Of the 269 patients with advanced NSCLC enrolled in the study, 93 (34.57%) had ILA, and 176 (65.43%) did not have ILA. Additionally, 39 (14.50%) of the patients developed CIP. The univariate analysis showed that pre-existing ILA [odds ratio (OR): 3.733; 95% confidence interval (CI): 1.846-7.549; P<0.001], body mass index (BMI) (≥24.12 kg/m²) (OR: 2.616; 95% CI: 1.312-5.214; P=0.006), and lactate dehydrogenase (LDH) (≥186.50 U/L) (OR: 2.231; 95% CI: 1.038-4.792; P=0.04) were highly correlated with CIP. In the multivariate analysis, ILA remained a robust independent predictor of CIP (OR: 4.128; 95% CI: 1.984-8.587; P<0.001). In terms of CIP, compared to the patients with mild CIP (grades 1/2), those with severe CIP (grades 3/4) had a worse OS (median for patients with grades 3/4: 12.4 months; median for patients with grades 1/2: 35.8 months) [hazard ratio (HR): 4.808; 95% CI: 1.671-13.830; P=0.004]. ILA was linked to a shorter OS time, such that the patients with ILA had a median OS of 21.1 months, while those without ILA had a median OS of 42.5 months (HR: 2.213; 95% CI: 1.404-3.488; P<0.001). The multivariable Cox regression analysis showed that ILA was also significantly associated with an increased risk of death (HR: 1.899; 95% CI: 1.253-2.878; P=0.002). However, no significant association was found between the PFTs before immunotherapy and CIP.

Conclusions: Pre-existing ILA is an independent risk factor that is strongly associated with CIP, and significantly correlated with worse PFS and OS in advanced NSCLC patients after first-line immunotherapy.