ICI Use in Patients with NSCLC After Radiotherapy Associated with Severe Pneumonitis

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Non–small-cell lung cancer (NSCLC) is the most common lung cancer and has a low 5-year survival rate.1 This low survival rate is attributed to the fact that approximately 70% of patients are initially diagnosed at an advanced stage.1 The traditional treatment recommendation for patients with advanced NSCLC has been chemotherapy with radiotherapy, which gives patients an overall survival of 12 to 18 months.1

Recent advancements in immunotherapy have greatly improved treatment for patients with NSCLC.1 Programmed cell death ligand 1 (PD-L1), programmed cell death 1 (PD-1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors are immune checkpoint inhibitors (ICIs) capable of enhancing antitumor activity and have become standard treatments for advanced NSCLC.1 PD-L1 is expressed on cancer cells and antigen-presenting cells.1 PD-1 is present on numerous cells, including activated T-cells, B-cells, natural-killer cells, macrophages, monocytes, and dendritic cells.1 CTLA-4 is a surface protein receptor.1 By inhibiting checkpoint pathways or molecules, ICIs promote tumor-cell death and boost immune system activity.1

Although generally better tolerated than traditional chemotherapy, immune-related adverse events (AEs), such as cutaneous lesions, hepatitis, colitis, myocarditis, inflammatory arthritis, and ICI-related pneumonitis, are commonly reported in patients treated with these drugs.1 Pneumonitis is particularly concerning in patients with NSCLC because these patients may have compromised pulmonary function due to tumor size and location along with other lung comorbidities.1 AEs associated with ICI use may become life-threatening for patients with NSCLC. Predicting which patients treated with ICIs will develop severe ICI-related pneumonitis is not currently possible.

To find clear predictors for developing severe ICI-related pneumonitis in patients with NSCLC, a retrospective study of 524 patients with lung cancer treated with ICIs was conducted between January 2017 and December 2021. Of the 524 patients, 55 were eventually diagnosed with ICI-related pneumonitis during this time period. These patients were divided into 2 groups after clinical and radiologic studies to determine pneumonitis severity: severe and non-severe. The severe group had 24 patients, and the non-severe group consisted of 31 patients. Further analysis indicated that there were no significant differences between the 2 groups in baseline characteristics, peripheral blood biomarkers, and clinical course. A difference in severity was seen in patients who had prior radiotherapy, however, and this was found to be an independent risk factor for the development of severe pneumonitis in patients with lung cancer treated with ICIs (P <.01).


  1. Zhang Q, Tang L, Zhou Y, He W, Li W. Immune checkpoint inhibitor-associated pneumonitis in non-small cell lung cancer: current understanding in characteristics, diagnosis, and management. Front Immunol. 2021;12:663986.

Source: Zhang Y, Zhang L, Zhong H. The risk factors of developing severity in immune checkpoint inhibitors-related pneumonitis in advanced lung cancer patients. Ann Oncol. 2022;33(2):S64.

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