Clinical characteristics and biomarkers of severe immune checkpoint inhibitor-related pneumonitis triggered by immunotherapy followed by radiation: a case report

Abstract

Background: The advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment landscape for tumor patients, dramatically improving survival rate. However, patients treated with immunotherapy are inevitably at risk of immune-related adverse events (irAEs). Immune checkpoint inhibitor-related pneumonitis (ICI-P) is an important type of IrAEs with a potentially lethal risk, which should be given more attention. Diagnosis and timely treatment of ICI-P is challenging due to the lack of specificity of its clinical and radiological features. Besides, poor understanding of biological mechanisms of ICI-P has led to a lack of reliable biomarkers to identify patients at risk, limiting timely treatment and proper management of it.

Case presentation: We presented longitudinal clinical features and successful treatment experience in a metastatic esophageal squamous cell carcinoma (ESCC) patient treated with immunochemotherapy followed by palliative radiotherapy for cervical lymph nodes who developed severe pneumonitis outside of the radiation field ten days after completion of radiotherapy suggestive of ICI-P. In addition, analysis of circulating biomarkers demonstrated an increase in platelet-to-lymphocyte ratio (PLR) and platelet-to-monocyte ratio (PMR), as well as the levels of CD4⁺T and CD8⁺T cells that tracked with the progression of ICI-P, and then decreased with corticosteroid treatment.

Conclusions: Our data highlight the imaging manifestations associated with ICI-related pulmonary toxicity and describe the dynamics of the corresponding circulating markers. Although our results reveal that dynamic monitoring of PLR and PMR as well as the levels of CD4⁺T and CD8⁺T cells may predict the risk of ICI-P, further investigations are needed to elucidate the underlying molecular and biological mechanisms for better management of ICI-P.

Keywords: biomarkers; immune checkpoint inhibitor-related pneumonitis (ICI-P); immune checkpoint inhibitors (ICIs); immune-related adverse event (irAE); immunotherapy; pneumonitis.

Figure 1

(A) CT image demonstrated cervical metastatic lymph nodes (on May 29, 2023). (B) CT image showed that cervical metastatic lymph nodes achieved partial remission about two months after the initial camrelizumab administration (on August 17, 2023). CT image revealed that metastatic lymph nodes in the neck achieved partial remission were further reduced nearly 4 months after the end of radiotherapy (follow-up on February 26, 2024). (D–F) Radiation field.

Figure 2

(A) Chest CT images about two months after the initial camrelizumab administration (on August 17, 2023). (B) Chest CT images about 1 week before radiotherapy (on September 18, 2023). (C) Chest CT images approximately 23 weeks after the initial camrelizumab administration and two weeks after the end of radiotherapy (on November 20, 2023). (D) Chest CT images during the significant remission of ICI-P (follow-up on February 26, 2024).

Figure 3

Timeline of the major treatment process and CT evaluation of this case.

Figure 4

Timeline indicates changes in PMR and PLR (A) as well as the levels of CD4⁺T and CD8⁺T cells (B) over the course of ICI-P.