Immune Checkpoint Inhibitor-associated Pneumonitis: A Narrative Review

Immune checkpoint inhibitors (ICI), such as pembrolizumab, nivolumab, durvalumab and ipilimumab, have significantly enhanced survival rates for multiple cancer types such as non-small cell lung cancer, melanoma, Hodgkin lymphoma, and breast cancer, and they have emerged as an adjunct or primary ther...

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Main Authors: Chang Li, Saadia A. Faiz, Megan Boysen-Osborn, Ajay Sheshadri, Monica K. Wattana
Format: Article
Language:English
Published: eScholarship Publishing, University of California 2025-02-01
Series:Western Journal of Emergency Medicine
Online Access:https://escholarship.org/uc/item/8jb3v6kf
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author Chang Li
Saadia A. Faiz
Megan Boysen-Osborn
Ajay Sheshadri
Monica K. Wattana
author_facet Chang Li
Saadia A. Faiz
Megan Boysen-Osborn
Ajay Sheshadri
Monica K. Wattana
author_sort Chang Li
collection DOAJ
description Immune checkpoint inhibitors (ICI), such as pembrolizumab, nivolumab, durvalumab and ipilimumab, have significantly enhanced survival rates for multiple cancer types such as non-small cell lung cancer, melanoma, Hodgkin lymphoma, and breast cancer, and they have emerged as an adjunct or primary therapy for malignant disease. Approximately 40% of patients with cancer on ICI therapy experience side effects called immune-related adverse events (irAE). While not the most common, pulmonary toxicities can be rapidly progressive, potentially fatal, and pose a three-fold increased risk for requiring intensive care unit-level of care. Pneumonitis is a focal or diffuse inflammation of the lung parenchyma, and clinical manifestations may be highly variable. While the onset is generally observed 6–12 weeks after the initiation of therapy, drug toxicity can develop rapidly within days after the first infusion or many months into therapy. Pneumonitis symptoms can be subtle or non-specific; therefore, a thorough and systematic evaluation considering other possible etiologies is crucial. Moreover, extrapulmonary findings, such as skin lesions, colitis, or endocrinopathies, should raise suspicion for irAE as drug toxicity can affect multiple organs simultaneously. Due to the significant overlap of clinical features between ICI-associated pneumonitis and respiratory infections, it can be challenging to differentiate the two conditions based on clinical presentation alone. A multidisciplinary approach to management is recommended for the treatment of ICI-associated pneumonitis, and classification of severity helps to guide interventions. Treatment options in more severe cases include systemic immunosuppression. Given the increased use of ICIs and greater probability that patients with ICI-associated pneumonitis will be seen in the emergency department, we aimed to provide a comprehensive framework for the diagnosis and management. In addition, identifying potential challenges in diagnosis and/or other contributors of respiratory symptoms and radiographic manifestations is highlighted.
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spelling doaj-art-1c527c29fc824b968f27b34e61d25a5c2025-08-20T03:42:22ZengeScholarship Publishing, University of CaliforniaWestern Journal of Emergency Medicine1936-900X1936-90182025-02-0126221021810.5811/westjem.2030520305Immune Checkpoint Inhibitor-associated Pneumonitis: A Narrative ReviewChang Li0Saadia A. Faiz1Megan Boysen-Osborn2Ajay Sheshadri3Monica K. Wattana4McGovern Medical School at University of Texas Health, Divisions of Pulmonary, Critical Care Medicine and Sleep Medicine, Houston, TexasThe University of Texas MD Anderson Cancer Center, Department of Pulmonary Medicine, Houston, TexasUniversity of California Irvine School of Medicine, Department of Emergency Medicine, Irvine, CaliforniaThe University of Texas MD Anderson Cancer Center, Department of Pulmonary Medicine, Houston, TexasThe University of Texas MD Anderson Cancer Center, Department of Emergency Medicine, Houston, TexasImmune checkpoint inhibitors (ICI), such as pembrolizumab, nivolumab, durvalumab and ipilimumab, have significantly enhanced survival rates for multiple cancer types such as non-small cell lung cancer, melanoma, Hodgkin lymphoma, and breast cancer, and they have emerged as an adjunct or primary therapy for malignant disease. Approximately 40% of patients with cancer on ICI therapy experience side effects called immune-related adverse events (irAE). While not the most common, pulmonary toxicities can be rapidly progressive, potentially fatal, and pose a three-fold increased risk for requiring intensive care unit-level of care. Pneumonitis is a focal or diffuse inflammation of the lung parenchyma, and clinical manifestations may be highly variable. While the onset is generally observed 6–12 weeks after the initiation of therapy, drug toxicity can develop rapidly within days after the first infusion or many months into therapy. Pneumonitis symptoms can be subtle or non-specific; therefore, a thorough and systematic evaluation considering other possible etiologies is crucial. Moreover, extrapulmonary findings, such as skin lesions, colitis, or endocrinopathies, should raise suspicion for irAE as drug toxicity can affect multiple organs simultaneously. Due to the significant overlap of clinical features between ICI-associated pneumonitis and respiratory infections, it can be challenging to differentiate the two conditions based on clinical presentation alone. A multidisciplinary approach to management is recommended for the treatment of ICI-associated pneumonitis, and classification of severity helps to guide interventions. Treatment options in more severe cases include systemic immunosuppression. Given the increased use of ICIs and greater probability that patients with ICI-associated pneumonitis will be seen in the emergency department, we aimed to provide a comprehensive framework for the diagnosis and management. In addition, identifying potential challenges in diagnosis and/or other contributors of respiratory symptoms and radiographic manifestations is highlighted.https://escholarship.org/uc/item/8jb3v6kf
spellingShingle Chang Li
Saadia A. Faiz
Megan Boysen-Osborn
Ajay Sheshadri
Monica K. Wattana
Immune Checkpoint Inhibitor-associated Pneumonitis: A Narrative Review
Western Journal of Emergency Medicine
title Immune Checkpoint Inhibitor-associated Pneumonitis: A Narrative Review
title_full Immune Checkpoint Inhibitor-associated Pneumonitis: A Narrative Review
title_fullStr Immune Checkpoint Inhibitor-associated Pneumonitis: A Narrative Review
title_full_unstemmed Immune Checkpoint Inhibitor-associated Pneumonitis: A Narrative Review
title_short Immune Checkpoint Inhibitor-associated Pneumonitis: A Narrative Review
title_sort immune checkpoint inhibitor associated pneumonitis a narrative review
url https://escholarship.org/uc/item/8jb3v6kf
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AT ajaysheshadri immunecheckpointinhibitorassociatedpneumonitisanarrativereview
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