ObjectiveTo develop and validate a Nomogram for predicting severe immune-related adverse events (irAEs) in patients with advanced non-small cell lung cancer (NSCLC) undergoing immunotherapy based on clinical features and inflammatory indicators. MethodsA total of 423 patients with advanced NSCLC treated with immunotherapy between January 2023 and January 2025 at Tianjin Fourth Center Hospital and Tianjin Cancer Hospital Airport Hospital were enrolled. Patients were divided into a severe irAEs group (≥grade 3, n=76) and a non-severe irAEs group (n=347), then randomly allocated into training and validation cohorts (7:3 ratio) . Clinical data, neutrophil-to-lymphocyte ratio (NLR), and interleukin-6/C-reactive protein (IL-6/CRP) levels were collected. Independent risk factors for severe irAEs during immunotherapy in advanced NSCLC were identified through logistic regression analysis, and a nomogram model was constructed accordingly. The discriminative ability, accuracy, and clinical utility of the model were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). ResultsAmong the 423 included patients [274 males, 149 females, aged 44-78 (60.77±5.91) years], the overall incidence of irAEs was 57.92% (245/423), with severe irAEs occurring in 17.97% (76/423). Multivariate analysis revealed that Eastern Cooperative Oncology Group (ECOG) performance score ≥2, programmed death-ligand 1 (PD-L1) expression [tumor proportion score (TPS) ≥50%], combination therapy regimen, low NLR values, and high IL-6/CRP ratio were independent risk factors for severe irAEs during immunotherapy in advanced NSCLC (P<0.05). The area under the ROC curve (AUC) was 0.948 [95%CI (0.912, 0.985)] in the training cohort and 0.946 [95%CI (0.917, 0.976)] in the validation cohort. Calibration curves and DCA demonstrated good consistency and clinical net benefit of the model. ConclusionThe nomogram integrating clinical features and inflammatory markers effectively predicts the risk of severe irAEs in advanced NSCLC patients receiving immunotherapy, exhibiting excellent discrimination, calibration, and clinical practicality.
Most immune-related adverse event (irAE) associated with immune checkpoint inhibitors (ICIs) resulted from excessive immune response against normal organs. The severity, timing, and organs affected by these events were often unpredictable. Adverse reactions could cause treatment delays or interruptions, in rare cases, pose a life-threatening risk. The mechanisms underlying irAE involved immune cell dysregulation, imbalances in inflammatory factor expression, alterations in autoantibodies and complement activation, even dysbiosis of intestinal microorganisms. However, the mechanisms of irAE occurrence might differ slightly among organs due to variations in their structures and the functions of resident immune cells. Future research should focus on the development of targeted drugs for the prevention or treatment of irAE based on the mechanisms by which irAE occurs in different organs. A deeper understanding of the mechanisms underlying irAE occurrence would aid clinicians in effectively utilizing ICIs and provide valuable guidance for their clinical application.
Objective Risk factors for real-word immune checkpoint inhibitor-related pneumonitis in patients with lung cancer were analyzed by systematic analysis. Methods Computerized retrieval of PubMed, EMbase, Web of Science, the Cochrane Library , WanFang Data, CNKI and VIP databases was carried out. Studies were collected from the database establishment to March 2023. Three researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.4.1software. Results A total of 18 studies were included with a total of 4 990 patients. The results of meta-analysis showed that, interstitial pneumonia [odds ratio (OR)=9.32, 95% confidence interval (CI) 4.66 - 18.67, P<0.01], smoking history (OR=2.39, 95%CI 1.29 - 4.45, P<0.01), chronic obstructive pulmonary disease (COPD) (OR=5.54, 95%CI 2.96 - 10.36, P<0.01), chest radiotherapy (OR=2.74, 95%CI 1.80 - 4.19, P<0.01), pulmonary fibrosis (OR=7.46, 95%CI 4.25 - 13.09, P<0.01), high programmed death ligand 1 (PD-L1) expression (OR=2.98, 95%CI 1.71 - 5.22, P<0.01), high absolute eosinophil count (AEC) (OR=3.92, 95%CI 2.17 - 7.08, P<0.01) and pembrolizumab (OR=2.90, 95%CI 1.56 - 5.37, P<0.01) were independent risk factors for immune checkpoint inhibitor-related pneumonitis in lung cancer patients. Conclusions Interstitial pneumonia, smoking history, COPD, Chest radiotherapy, pulmonary fibrosis, high PD-L1expression, high AEC and pembrolizumab are independent risk factors for immune checkpoint inhibitor-related pneumonitis in lung cancer patients. Due to insufficient evidence on the risk factors of low albumin, more studies are needed to further identify it.
In December 2019, an outbreak of pneumonia associated with the coronavirus disease 2019 (COVID-19) occurred in Wuhan, China. The lung imaging finding is like that of the lung cancer immune checkpoint inhibitors (ICI) associated pneumonia. Therefore, we speculated that they may have similar pathogenesis and treatment strategies, which is reviewed in this article in order to provide some reference to timely and effectively reduce the fatality rate of COVID-19.