How is immunotherapy-induced pneumonitis treated?

Treatment of Immunotherapy-Induced Pneumonitis

Immunotherapy-induced pneumonitis should be treated with corticosteroids as the primary therapy, with the dosage and route of administration determined by the severity grade, and additional immunosuppressive agents should be added if there is no improvement within 48 hours of high-dose steroids for severe cases. 1

Diagnosis and Assessment

Before initiating treatment, it's essential to:

• Obtain a CT scan for any patient with respiratory symptoms (cough, shortness of breath, chest pain, fever, increased oxygen requirements) 2
• Consider bronchoscopy with bronchoalveolar lavage to rule out infection, especially in grade 2 or higher pneumonitis 1
• Note that radiological features may include ground glass opacities, organizing pneumonia pattern, interstitial pneumonia pattern, or hypersensitivity pneumonitis-like changes 1, 2

Treatment Algorithm Based on Severity

Grade 1 (Asymptomatic, radiographic findings only):

• Consider holding immunotherapy
• Monitor symptoms every 2-3 days
• Repeat chest CT prior to next scheduled dose 2

Grade 2 (Symptomatic, mild to moderate):

• Hold immunotherapy
• Start oral corticosteroids: prednisone 1 mg/kg/day or equivalent 1
• Clinically assess every 2-3 days and monitor radiologically 1
• If no improvement within 48-72 hours, treat as Grade 3 2
• Taper steroids over 4-6 weeks after recovery 1
• Delay reintroduction of immunotherapy until prednisone dose ≤10 mg/day 1

Grade 3-4 (Severe symptoms, limiting self-care, life-threatening):

• Permanently discontinue immunotherapy 1, 2
• Hospitalize the patient 1
• Administer high-dose intravenous corticosteroids: methylprednisolone 2-4 mg/kg/day or equivalent 1
• If no improvement after 48 hours, add additional immunosuppressive therapy 1, 2:
  • Options include infliximab, mycophenolate mofetil, or cyclophosphamide 1
• Consider broad-spectrum antibiotics if infection cannot be reliably excluded 1
• Taper steroids very slowly over 6 weeks or more 1

Special Considerations

Chronic Immunotherapy Pneumonitis

• Approximately 2% of patients develop chronic pneumonitis requiring ≥12 weeks of immunosuppression 3
• Recrudescence typically occurs when steroids are tapered to ≤10 mg prednisone 3
• These patients may require prolonged steroid therapy (median 37 weeks) 3
• Characterized by persistent bronchoalveolar lavage fluid lymphocytosis and organizing pneumonia pattern on biopsy 3

Monitoring and Follow-up

• Regular follow-up imaging is necessary to confirm resolution 2
• Re-emergence of pneumonitis typically occurs in the same locations on chest CT 3
• Monitor for steroid-related complications during prolonged treatment courses

Risk Factors to Consider

• Combination immunotherapy carries higher risk (10% vs 3% for monotherapy) 1, 2
• Pre-existing lung disease may increase risk and complicate diagnosis 2, 4
• Prior thoracic radiation may increase risk for pneumonitis development 4

Pitfalls and Caveats

• Pneumonitis is one of the most common causes of immune checkpoint inhibitor-related death 2
• Concurrent immune-related adverse events may occur in up to 50% of patients with pneumonitis 2
• Distinguishing between COVID-19 pneumonia and immunotherapy-induced pneumonitis can be challenging during the pandemic 5
• Relapses of pneumonitis during steroid tapering are common, requiring careful monitoring 1
• Radiographic features of immunotherapy-induced pneumonitis differ from chemotherapy-induced pneumonitis, with the former showing more specific features including consolidation, ground glass opacities, and septal thickening 6