Immune Checkpoint Inhibitor-associated Pneumonitis: A Narrative Review.

in The western journal of emergency medicine by Chang Li, Saadia A Faiz, Megan Boysen-Osborn, Ajay Sheshadri, Monica K Wattana

TLDR

  • Immune checkpoint inhibitors have improved cancer survival rates but also increase the risk of immune-related adverse events, including pneumonitis, which can be rapidly progressive and potentially fatal.
  • ICI-associated pneumonitis can be challenging to diagnose and requires a multidisciplinary approach to management, with classification of severity guiding interventions.
  • Better diagnosis and management strategies are needed to minimize treatment delays and improve patient outcomes for ICI-associated pneumonitis.

Abstract

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.

Overview

  • The study focuses on the management of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs), specifically pulmonary toxicities such as pneumonitis.
  • The study emphasizes the importance of a multidisciplinary approach to management and the need for a comprehensive framework for diagnosis and treatment.
  • The study aims to provide guidance for healthcare professionals on how to diagnose and manage ICI-associated pneumonitis, particularly in emergency department settings.

Comparative Analysis & Findings

  • ICIs have significantly improved survival rates for various cancer types, but approximately 40% of patients experience irAEs, including pulmonary toxicities like pneumonitis.
  • ICI-associated pneumonitis can develop rapidly within days of the first infusion or months into therapy, with symptoms often being subtle or non-specific.
  • Classification of severity helps guide interventions, and more severe cases may require systemic immunosuppression.

Implications and Future Directions

  • The study highlights the need for better diagnosis and management strategies for ICI-associated pneumonitis to minimize treatment delays and improve patient outcomes.
  • Future research should focus on developing predictive biomarkers for ICI toxicity and exploring potential mechanisms for preventing or mitigating pulmonary adverse events.
  • Clinicians should be aware of the increased risk of pulmonary toxicities in patients receiving ICIs and be prepared to aggressively manage symptoms and complications.
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