From the Guidelines
Immunotherapy for cancer can cause acute respiratory issues, most notably immune-related pneumonitis, with a significantly higher risk in combination therapy as compared to chemotherapy alone, as evidenced by a relative risk of 2.79 [2.09; 3.74] 1.
Key Respiratory Complications
- Immune-related pneumonitis: inflammation of the lung tissue, which can present with symptoms such as shortness of breath, cough, chest pain, fever, or hypoxemia, and may occur at any time during treatment 1.
- Upper airway inflammation
- Pleural effusions
- Sarcoid-like granulomatous reactions
Management and Risk Factors
The management of these complications depends on their severity, with mild cases requiring monitoring, moderate cases treated with corticosteroids (such as prednisone 1-2 mg/kg/day), and severe cases necessitating high-dose steroids plus additional immunosuppressants 1. Checkpoint inhibitors like nivolumab, atezolizumab, and ipilimumab are commonly associated with these effects, with combination therapy (including chemotherapy and immunotherapy) carrying a higher risk than monotherapy, as shown by the increased relative risk of pneumonitis in the combination arm 1.
Clinical Implications
It is crucial for clinicians to be aware of these potential respiratory complications when administering immunotherapy for cancer, especially in combination regimens, to promptly identify and manage them, thereby minimizing morbidity, mortality, and impact on quality of life 1.
From the FDA Drug Label
Respiratory, Thoracic and Mediastinal Coughd 20 0.2 21 0.4 Dyspneae 12 0.8 12 0.4 ... Pneumoniai 13 5 14 8 10 2.6
The most frequent serious adverse reactions reported in ≥2% of patients who received OPDIVO with chemotherapy were pneumonia (11%), dysphagia (7%), esophageal stenosis (2.9%), acute kidney injury (2.9%), and pyrexia (2.3%). The most frequent serious adverse reactions reported in ≥2% of patients who received OPDIVO with ipilimumab were pneumonia (10%), pyrexia (4.3%), pneumonitis (4%), aspiration pneumonia (3.7%), dysphagia (3.7%)...
The acute respiratory issues caused by immunotherapy for cancer include:
- Cough
- Dyspnea
- Pneumonia
- Pneumonitis
- Aspiration pneumonia 2
From the Research
Respiratory Issues Caused by Immunotherapy for Cancer
- Immunotherapy for cancer can cause various respiratory issues, including pneumonitis, which is a focal or diffuse inflammation of the lung parenchyma 3.
- Pneumonitis is a well-described immune-related adverse event that can be particularly concerning in patients receiving immunotherapy for non-small-cell lung cancer 4, 5.
- The clinical manifestations of pneumonitis can be highly variable, and symptoms can be subtle or non-specific, making diagnosis challenging 3.
- Risk factors for severe immune-related pneumonitis include pre-existing fibrosis, emphysematous changes, low diffusing capacity for carbon monoxide (%DLCO), and high surfactant protein D (SP-D) level 6.
- Squamous cell carcinoma, baseline %DLCO, and SP-D level have been identified as significant risk factors for severe pneumonitis in patients receiving immunotherapy for non-small-cell lung cancer 6.
Acute Respiratory Issues
- Acute respiratory issues caused by immunotherapy for cancer can be rapidly progressive and potentially fatal, posing a significant challenge in the treatment of cancer patients 3.
- Pulmonary toxicities, including pneumonitis, can cause significant disruptions in the treatment of cancer and may require intensive care unit-level of care 5, 3.
- The onset of pneumonitis can occur within days after the first infusion or many months into therapy, and symptoms can be highly variable, making early detection and management crucial 3.
Diagnosis and Management
- Diagnosis of immunotherapy-associated pneumonitis requires a thorough and systematic evaluation, considering other possible etiologies, and a multidisciplinary approach to management is recommended 3, 7.
- Classification of severity helps guide interventions, and treatment options in more severe cases include systemic immunosuppression 3.
- Identifying potential challenges in diagnosis and other contributors of respiratory symptoms and radiographic manifestations is essential for optimal care 3, 7.