What are the causes of induced pneumonitis (inflammation of the lungs)?

From the Guidelines

Amidst one induced pneumonitis, the primary management approach is immediate discontinuation of the offending agent, and corticosteroid therapy is typically recommended, with a dose of prednisone 40-60 mg daily for 2-6 months followed by a slow taper based on clinical response, as supported by the most recent study from 2021 1. The condition occurs due to direct cytotoxic effects and immune-related adverse events caused by the accumulation of immune checkpoint inhibitors in lung tissue, with risk increasing with higher doses, longer duration of therapy, and pre-existing lung disease. Some key points to consider in the management of pneumonitis include:

• The incidence of pneumonitis associated with PD-1/PDL-1 and CTLA-4-targeted therapies is <5%, with high-grade (≥grade 3) events occurring in 1–2% of patients, as reported in a study from 2017 1.
• Higher rates have been reported for combinations of PD-1 and CTLA-4 inhibitors, and in patients with non-small cell lung cancer (NSCLC) compared to patients with melanoma.
• Pneumonitis may present on imaging studies as cryptogenic organizing pneumonia (COP), nonspecific interstitial pneumonitis (NSIP), hypersensitivity pneumonitis (HP), or usual interstitial pneumonitis (UIP)/pulmonary fibrosis (PF).
• Clinical and radiographic findings of ICI-related pneumonitis may closely mimic pneumonia, lymphangitic spread of disease, cancer progression, and diffuse alveolar hemorrhage.
• Supportive care includes supplemental oxygen as needed and respiratory support, and alternative treatments should be considered for the underlying condition.
• Pulmonary function tests and high-resolution CT scans are essential for diagnosis and monitoring recovery, as shown in a study from 2021 1.
• Recovery may take months, and some patients may develop permanent fibrosis despite appropriate management.

From the FDA Drug Label

Pneumonitis, pulmonary fibrosis, pulmonary veno-occlusive disease and other forms of pulmonary toxicity leading to respiratory failure have been reported during and following treatment with cyclophosphamide. Late onset pneumonitis (greater than 6 months after start of cyclophosphamide) appears to be associated with increased mortality Pneumonitis may develop years after treatment with cyclophosphamide. Monitor patients for signs and symptoms of pulmonary toxicity.

The patient should be monitored for signs and symptoms of pulmonary toxicity, including pneumonitis, as it may develop during or after treatment with cyclophosphamide 2.

• Key points:
  • Pneumonitis may occur during or after cyclophosphamide treatment
  • Monitor patients for signs and symptoms of pulmonary toxicity
  • Late onset pneumonitis is associated with increased mortality
  • Pneumonitis may develop years after treatment with cyclophosphamide 2.

From the Research

Induced Pneumonitis Treatment

• The use of corticosteroids in treating pneumonia has been studied extensively, with varying results depending on the severity and type of pneumonia 3, 4, 5, 6.
• In cases of severe community-acquired pneumonia, corticosteroids have been shown to reduce mortality, the need for invasive mechanical ventilation, and ICU admission 4, 5.
• However, the evidence for using corticosteroids in less severe cases of pneumonia is less clear, with some studies suggesting no significant benefit 4, 5.
• The optimal dose and duration of corticosteroid therapy for pneumonia is still a topic of debate, with one study suggesting an optimal dose of approximately 6 mg of dexamethasone (or equivalent) for a duration of 7 days 5.
• Corticosteroids may increase the risk of hyperglycemia, superinfections, and increased length-of-stay in patients with pneumonia 4, 6.

Immune Checkpoint Inhibitor-Induced Pneumonitis

• Immune checkpoint inhibitors (ICIs) have been associated with an increased risk of pneumonitis, with an incidence of 6.4% in one retrospective study 7.
• The clinical characteristics and outcomes of ICI-induced pneumonitis can vary, with some patients requiring hospital admission and ICU care 7.
• The risk factors for overall survival in patients who develop pneumonitis after receiving ICIs include the type of ICI agent used, prior chemotherapy, and lack of cancer-related surgery 7.

Corticosteroid Use in Specific Types of Pneumonia

• Corticosteroids are recommended for use in Pneumocystis jiroveci pneumonia in HIV-infected patients, but not for influenza pneumonia 6.
• The use of corticosteroids in other types of severe community-acquired pneumonia is not supported by strong evidence, and further studies are needed to identify subgroups that may benefit from this treatment 6.