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

• Published in: Clinical lung cancer 2024-11, Vol.25 (7), p.624-633.e2
• Main Authors: Soto-Lanza, Felipe, Glick, Lydia, Chan, Colin, Zhong, Linda, Wilson, Nathaniel, Faiz, Saadia, Gandhi, Saumil, Naing, Aung, Heymach, John V., Shannon, Vickie R., Franco-Vega, Maria, Liao, Zhongxing, Lin, Steven H., Palaskas, Nicolas L., Wu, Jia, Shroff, Girish S., Altan, Mehmet, Sheshadri, Ajay
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Cancer survivorship; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Female; Follow-Up Studies; Humans; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Interstitial lung abnormalities; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Middle Aged; Pneumonia - chemically induced; Pneumonia - etiology; Pneumonia - mortality; Radiological resolution; Retrospective Studies; Steroid-refractory; Steroid-resistant; Survival Rate
• ISSN: 1525-7304; 1938-0690; 1938-0690
• DOI: 10.1016/j.cllc.2024.07.017

•At 1-year, mortality is increased in steroid-refractory, but not steroid-resistant or steroid-dependent pneumonitis.•Pretreatment interstitial lung abnormalities (ILAs) are associated with partial resolution of ICI pneumonitis.•Partial radiological resolution of immune checkpoint inhibitor (ICI) pneumonitis is associated with new or worsening pulmonary and persistent hypoxemia. Despite known short-term mortality risk of immune checkpoint inhibitor (ICI) pneumonitis, its impact on 1-year mortality, long-term pulmonary function, symptom persistence, and radiological resolution remains unclear. We retrospectively analyzed 71 nonsmall 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. Steroid-refractory pneumonitis (hazard ratio [HR] = 15.1, 95% confidence interval [95% CI]:3.9-57.8, P < .0001) was associated with higher 1-year mortality compared to steroid-responsive cases. However, steroid-resistant (odds ratio [OR] = 1.4, 95% CI: 0.4-5.1, P = .58) and steroid-dependent (OR = 0.4, 95% CI: 0.1-1.2, P = .08) pneumonitis were not. Nonadenocarcinoma histology (OR = 6.7, 95% CI: 1.6-46.6, P = .01), grade 3+ pneumonitis (OR = 4.6, 95% CI: 1.3-22.7, P = .03), and partial radiological resolution (OR = 6.3, 95% CI: 1.8-23.8, P = .004) were linked to increased pulmonary symptoms after pneumonitis resolution. Grade 3+ pneumonitis (OR = 8.1, 95% CI: 2.3-31.5, P = .001) and partial radiological resolution (OR = 5.45, 95% CI: 1.29-37.7, P = .03) associated with residual hypoxemia. Nonadenocarcinoma histology (OR = 3.6, 95% CI: 1.01-17.6, P = .06) and pretreatment ILAs (OR = 4.8, 95% CI: 1.14-33.09, P = .05) were associated with partial radiological resolution. Steroid refractory pneumonitis increases 1-year mortality in NSCLC patients. Pretreatment ILAs may signal predisposition to fibrosis-related outcomes, seen as partial resolution, which in turn is associated with postresolution symptoms and residual hypoxemia. These findings offer insights for identifying patients at risk of adverse outcomes post-pneumonitis resolution. Long-term outcomes after immune checkpoint inhibitor pneumonitis are not known. We performed a retrospective study of 71 patien