Long-term Clinical, Radiological, and Mortality Outcomes Following Pneumonitis in Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors: A Retrospective Analysis

Abstract

AimsDespite known short-term mortality risk of immune checkpoint inhibitor (ICI) pneumonitis, its impact on one-year mortality, long-term pulmonary function, symptom persistence, and radiological resolution remains unclear. MethodsWe retrospectively analyzed 71 non-small cell lung cancer (NSCLC) patients treated with anti-PD(L)1 monoclonal antibodies between 2018-2021, who developed pneumonitis. Clinical and demographic covariates were collected from electronic medical record. Cox regression assessed associations with mortality, while logistic regression evaluated associations with persistent symptoms, hypoxemia, and radiological resolution. ResultsSteroid-refractory pneumonitis (hazard ratio [HR]=15.1, 95% confidence interval [95%CI]:3.9-57.8, p<0.0001) was associated with higher one-year mortality compared to steroid-responsive cases. However, steroid-resistant (odds ratio [OR]=1.4, 95%CI:0.4-5.1, p=0.58) and steroid-dependent (OR=0.4, 95%CI: 0.1-1.2, p=0.08) pneumonitis were not. Non-adenocarcinoma histology (OR=6.7, 95%CI: 1.6-46.6, p=0.01), grade 3+ pneumonitis (OR=4.6, 95%CI: 1.3-22.7, p=0.03), and partial radiological resolution (OR=6.3, 95%CI: 1.8-23.8, p=0.004) were linked to increased pulmonary symptoms after pneumonitis resolution. Grade 3+ pneumonitis (OR=8.1, 95%CI: 2.3-31.5, p=0.001) and partial radiological resolution (OR=5.45, 95%CI:1.29-37.7, p=0.03) associated with residual hypoxemia. Non-adenocarcinoma histology (OR=3.6, 95%CI: 1.01-17.6, p=0.06) and pre-treatment ILAs (OR=4.8, 95% CI: 1.14-33.09, p=0.05) were associated with partial radiological resolution. ConclusionsSteroid refractory pneumonitis increases one-year mortality in NSCLC patients. Pre-treatment ILAs may signal predisposition to fibrosis-related outcomes, seen as partial resolution, which in turn is associated with post-resolution symptoms and residual hypoxemia. These findings offer insights for identifying patients at risk of adverse outcomes post-pneumonitis resolution. Micro AbstractLong-term outcomes after immune checkpoint inhibitor pneumonitis are not known. We performed a retrospective study of 71 patients with pneumonitis to fill in this gap. At one year, mortality is increased in steroid-refractory, but not steroid-resistant or steroid-dependent pneumonitis. Pre-treatment interstitial lung abnormalities (ILAs) are associated with partial resolution of ICI pneumonitis, which in turn is associated with new or worsening pulmonary and persistent hypoxemia.