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Respiratory Investigation Sep 2020Immune checkpoint inhibitors (ICIs) have been a breakthrough in medical oncology. However, many patients experience a novel type of adverse drug reaction that has a... (Review)
Review
Immune checkpoint inhibitors (ICIs) have been a breakthrough in medical oncology. However, many patients experience a novel type of adverse drug reaction that has a unique clinical presentation, called immune-related adverse events (irAEs). A breakdown of self-tolerance and an exaggerated autoimmune reaction by the host are assumed to be the underlying mechanisms. Therefore, special attention to the optimal diagnosis and management is required. Among the various effects of irAE, pneumonitis has been recognized as an important manifestation because of its high morbidity and mortality. As the application of ICIs is expanding to a wider variety of tumor types, as well as its use with cytotoxic agents and radiation, clinicians are highly likely to encounter this complication. In this review, we will summarize the current understanding of the underlying mechanisms, incidence, risk factors, optimal diagnostic workup, and management of ICI-related pneumonitis (IRP). We will also review fundamental information on drug-induced lung toxicity in the oncology setting. In addition, research perspectives focused on better risk stratification and management to avoid serious complications in the future are presented.
Topics: Antineoplastic Agents, Immunological; Autoimmunity; B7-H1 Antigen; CTLA-4 Antigen; Humans; Neoplasms; Pneumonia; Programmed Cell Death 1 Receptor
PubMed: 32713811
DOI: 10.1016/j.resinv.2020.05.008 -
Frontiers in Immunology 2023Immune checkpoint inhibitors (ICIs) modulate the body's immune function to treat tumors but may also induce pneumonitis. Immune checkpoint inhibitor-related pneumonitis... (Review)
Review
Immune checkpoint inhibitors (ICIs) modulate the body's immune function to treat tumors but may also induce pneumonitis. Immune checkpoint inhibitor-related pneumonitis (ICIP) is a serious immune-related adverse event (irAE). Immunotherapy is currently approved as a first-line treatment for non-small cell lung cancer (NSCLC), and the incidence of ICIP in NSCLC patients can be as high as 5%-19% in clinical practice. ICIP can be severe enough to lead to the death of NSCLC patients, but there is a lack of a gold standard for the diagnosis of ICIP. Radiomics is a method that uses computational techniques to analyze medical images (e.g., CT, MRI, PET) and extract important features from them, which can be used to solve classification and regression problems in the clinic. Radiomics has been applied to predict and identify ICIP in NSCLC patients in the hope of transforming clinical qualitative problems into quantitative ones, thus improving the diagnosis and treatment of ICIP. In this review, we summarize the pathogenesis of ICIP and the process of radiomics feature extraction, review the clinical application of radiomics in ICIP of NSCLC patients, and discuss its future application prospects.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Pneumonia; Immunotherapy
PubMed: 37799725
DOI: 10.3389/fimmu.2023.1251645 -
Journal of Thoracic Imaging Jan 2021Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current outbreak of Coronavirus disease 2019 (COVID-19). Although imaging should not... (Review)
Review
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current outbreak of Coronavirus disease 2019 (COVID-19). Although imaging should not be used for first-line screening or diagnosis, radiologists need to be aware of its imaging features, and those of common conditions that may mimic COVID-19 pneumonia. In this Pictorial Essay, we review frequently encountered conditions with imaging features that overlap with those that are typical of COVID-19 (including other viral pneumonias, chronic eosinophilic pneumonia, and organizing pneumonia), and those with features that are indeterminate for COVID-19 (including hypersensitivity pneumonitis, pneumocystis pneumonia, diffuse alveolar hemorrhage, pulmonary edema, and pulmonary alveolar proteinosis).
Topics: COVID-19; Diagnosis, Differential; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tomography, X-Ray Computed
PubMed: 32852419
DOI: 10.1097/RTI.0000000000000554 -
Frontiers in Immunology 2023Immune checkpoint inhibitor (ICI)-related pneumonitis (IRP) is a common and potentially fatal clinical adverse event. The identification and prediction of the risk of...
BACKGROUND
Immune checkpoint inhibitor (ICI)-related pneumonitis (IRP) is a common and potentially fatal clinical adverse event. The identification and prediction of the risk of ICI-related IRP is a major clinical issue. The objective of this study was to apply a machine learning method to explore risk factors and establish a prediction model.
METHODS
We retrospectively analyzed 48 patients with IRP (IRP group) and 142 patients without IRP (control group) who were treated with ICIs. An Elastic Net model was constructed using a repeated k-fold cross-validation framework (repeat = 10; k = 3). The prediction models were validated internally and the final prediction model was built on the entire training set using hyperparameters with the best interval validation performance. The generalizability of the final prediction model was assessed by applying it to an independent test set. The overall performance, discrimination, and calibration of the prediction model were evaluated.
RESULTS
Eleven predictors were included in the final predictive model: sindillizumab, number of ≥2 underlying diseases, history of lung diseases, tirelizumab, non-small cell lung cancer (NSCLC), percentage of CD4 lymphocytes, body temperature, KPS score ≤70, hemoglobin, cancer stage IV, and history of antitumor therapy. The external validation of the risk prediction model on an independent test set of 37 patients and showed good discrimination and acceptable calibration ability: with AUC of 0.81 (95% CI 0.58-0.90), AP of 0.76, scaled Brier score of 0.31, and Spiegelhalter-z of -0.29 (P-value:0.77). We also designed an online IRP risk calculator for use in clinical practice.
CONCLUSION
The prediction model of ICI-related IRP provides a tool for accurately predicting the occurrence of IRP in patients with cancer who received ICIs.
Topics: Humans; Immune Checkpoint Inhibitors; Carcinoma, Non-Small-Cell Lung; Retrospective Studies; Lung Neoplasms; Pneumonia; Machine Learning
PubMed: 37457722
DOI: 10.3389/fimmu.2023.1138489 -
The Oncologist Nov 2023Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially.
INTRODUCTION
Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially.
METHODS
We conducted a retrospective review of 419 patients with advanced non-small cell lung cancer (NSCLC) who were treated with anti-PD-(L)1 with or without anti-CTLA-4 therapy. Clinical, imaging, and microbiological data were evaluated by multidisciplinary adjudication teams. The primary outcome of interest was grade ≥2 (CTCAEv5) pneumonitis. Clinicopathologic variables, tobacco use, cancer therapies, and preexisting lung disease were assessed for univariate effects using Cox proportional hazards models. We created multivariate Cox proportional hazards models to assess risk factors for pneumonitis and mortality. Pneumonitis, pneumonia, and progression were modeled as time-dependent variables in mortality models.
RESULTS
We evaluated 419 patients between 2013 and 2021. The cumulative incidence of pneumonitis was 9.5% (40/419). In a multivariate model, pneumonitis increased the risk for mortality (HR 1.6, 95% CI, 1.0-2.5), after adjustment for disease progression (HR 1.6, 95% CI, 1.4-1.8) and baseline shortness of breath (HR 1.5, 95% CI, 1.2-2.0). Incomplete resolution was more common with more severe pneumonitis. Interstitial lung disease was associated with higher risk for pneumonitis (HR 5.4, 95% CI, 1.1-26.6), particularly in never smokers (HR 26.9, 95% CI, 2.8-259.0).
CONCLUSION
Pneumonitis occurred at a high rate and significantly increased mortality. Interstitial lung disease, particularly in never smokers, increased the risk for pneumonitis.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Incidence; Lung Neoplasms; Pneumonia; Risk Factors; Lung Diseases, Interstitial; Retrospective Studies
PubMed: 37156009
DOI: 10.1093/oncolo/oyad118 -
Expert Opinion on Biological Therapy Sep 2020The COVID-19 pandemic occurred amid the cancer immunotherapy revolution. Immune checkpoint inhibitors (ICIs) have become the standard of care for several solid cancers...
INTRODUCTION
The COVID-19 pandemic occurred amid the cancer immunotherapy revolution. Immune checkpoint inhibitors (ICIs) have become the standard of care for several solid cancers and are associated with peculiar toxicities, including pneumonitis which has similar features to COVID-19 pneumonia.
AREAS COVERED
We summarize the main hallmarks of lung injury induced by ICIs and severe acute respiratory syndrome coronavirus 2 and discuss the critical aspects for differential diagnosis and management. Symptoms and radiological findings are often similar; conversely, treatments are quite different. Furthermore, we focus on potential interactions generating hypotheses that need confirmatory studies.
EXPERT OPINION
All cancer patients treated with immunotherapy should receive screening for SARS-CoV-2. This would improve the diagnosis and management of pneumonia and guide therapeutic choices. Furthermore, clinicians could estimate the risk/benefit of continuing ICI treatment in COVID-19 positive patients. Temporary withdrawal of the immunotherapy treatment pending resolution of viral infection may be a reasonable option in long-responders patients.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Diagnosis, Differential; Disease Management; Humans; Immunotherapy; Neoplasms; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32588674
DOI: 10.1080/14712598.2020.1789097 -
BMJ Case Reports Jul 2021Pembrolizumab is a selective anti-PD-L1 humanised monoclonal antibody approved by the Food and Drug Administration for treating multiple cancers, including cervical...
Pembrolizumab is a selective anti-PD-L1 humanised monoclonal antibody approved by the Food and Drug Administration for treating multiple cancers, including cervical cancer, non-small cell lung cancer (NSCLC), renal cell carcinoma, bladder cancer, and squamous head and neck cancer. Pneumonitis is a rare but known complication of pembrolizumab treatment for NSCLC. The median time frame of its appearance is 2.8 months. However, we present a case of pneumonitis appearing within 48 hours. The patient presented with rapidly progressive respiratory failure, and imaging demonstrated diffuse bilateral patchy involvement of the upper lung lobe and pre-hilar regions, which likely indicate pneumonitis. Because of likely grade 3 pneumonitis, he was treated with steroids and showed immediate improvement of symptoms. Repeated CT imaging showed resolution of bilateral patchy infiltrates. He was discharged to the rehabilitation unit. Rapid recognition of pneumonitis as a side effect of pembrolizumab is important because early treatment can help prevent respiratory failure and possible death.
Topics: Antibodies, Monoclonal, Humanized; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Male; Pneumonia
PubMed: 34266820
DOI: 10.1136/bcr-2021-242493 -
Respiratory Medicine and Research Nov 2022Anticancer immune-checkpoint inhibitors (ICI) can cause immune-related adverse events (irAEs), including interstitial pneumonitis, which is managed chiefly with systemic...
BACKGROUND
Anticancer immune-checkpoint inhibitors (ICI) can cause immune-related adverse events (irAEs), including interstitial pneumonitis, which is managed chiefly with systemic corticosteroids. When corticosteroids fail, second-line immunosuppressive therapy is indicated. Our objective was to evaluate the prevalence and outcomes of ICI-induced pneumonitis requiring second-line immunosuppressive therapy (IS).
METHODS
We collected data form the REISAMIC pharmacovigilance registry and the multidisciplinary immunological toxicity board at Gustave Roussy (France). No response to steroids was called steroid-refractory pneumonitis and relapse after an initial response was defined as steroid-resistant pneumonitis.
RESULTS
Of the 1187 patients screened from the REISAMIC register, 48 (4%) patients had pneumonitis treated with corticosteroids. Five of them (10%) had corticosteroid refractory/resistant disease but only 2 were treated with immunosuppressive therapy. Four additional patients requiring immunosuppressive therapy identified via the immunological toxicity board were included. Immunosuppressive therapy were cyclophosphamide (n=4 pts), infliximab (n=1 pt), intravenous immunoglobulins (n=1 pt). Five of these six patients had corticosteroid-refractory disease and one had corticosteroid-resistant pneumonitis. Five patients had severe pneumonitis (Common Terminology Criteria for Adverse Events grade ≥3) at initial pneumonitis diagnosis. Two months mortality rate in patients treated with IS was 67% (4/6). Among the patients treated with IS, the two patients alive at 5 months were treated with cyclophosphamide.
CONCLUSION
Patients with ICI-pneumonitis treated by steroids received IS in 10% of cases. High mortality at 67% of patients was observed in ICI-pneumonitis after steroid failure. Cyclophosphamide could be a treatment option for pneumonitis after corticosteroid failure that requires further investigations.
Topics: Humans; Immune Checkpoint Inhibitors; Prevalence; Immunosuppressive Agents; Cyclophosphamide; Pneumonia; Adrenal Cortex Hormones
PubMed: 36370683
DOI: 10.1016/j.resmer.2022.100969 -
Frontiers in Immunology 2023Immune checkpoint inhibitors (ICI) may cause pneumonitis, resulting in potentially fatal lung inflammation. However, distinguishing pneumonitis from pneumonia is...
Heterogenous lung inflammation CT patterns distinguish pneumonia and immune checkpoint inhibitor pneumonitis and complement blood biomarkers in acute myeloid leukemia: proof of concept.
BACKGROUND
Immune checkpoint inhibitors (ICI) may cause pneumonitis, resulting in potentially fatal lung inflammation. However, distinguishing pneumonitis from pneumonia is time-consuming and challenging. To fill this gap, we build an image-based tool, and further evaluate it clinically alongside relevant blood biomarkers.
MATERIALS AND METHODS
We studied CT images from 97 patients with pneumonia and 29 patients with pneumonitis from acute myeloid leukemia treated with ICIs. We developed a CT-derived signature using a habitat imaging algorithm, whereby infected lungs are segregated into clusters ("habitats"). We validated the model and compared it with a clinical-blood model to determine whether imaging can add diagnostic value.
RESULTS
Habitat imaging revealed intrinsic lung inflammation patterns by identifying 5 distinct subregions, correlating to lung parenchyma, consolidation, heterogenous ground-glass opacity (GGO), and GGO-consolidation transition. Consequently, our proposed habitat model (accuracy of 79%, sensitivity of 48%, and specificity of 88%) outperformed the clinical-blood model (accuracy of 68%, sensitivity of 14%, and specificity of 85%) for classifying pneumonia versus pneumonitis. Integrating imaging and blood achieved the optimal performance (accuracy of 81%, sensitivity of 52% and specificity of 90%). Using this imaging-blood composite model, the post-test probability for detecting pneumonitis increased from 23% to 61%, significantly ( = 1.5 - 9) higher than the clinical and blood model (post-test probability of 22%).
CONCLUSION
Habitat imaging represents a step forward in the image-based detection of pneumonia and pneumonitis, which can complement known blood biomarkers. Further work is needed to validate and fine tune this imaging-blood composite model and further improve its sensitivity to detect pneumonitis.
Topics: Humans; Immune Checkpoint Inhibitors; Pneumonia; Tomography, X-Ray Computed; Inflammation; Biomarkers; Leukemia, Myeloid, Acute
PubMed: 37841255
DOI: 10.3389/fimmu.2023.1249511 -
Journal of the American College of... Apr 2021
Topics: Heart Failure; Humans; Pneumonia
PubMed: 33888246
DOI: 10.1016/j.jacc.2021.03.010