Is pneumonitis more likely with Katruda (medication name unknown, possibly referring to a brand name, e.g. Keytruda (pembrolizumab))?

Pneumonitis Risk with Keytruda (Pembrolizumab)

Yes, pneumonitis is more likely with Keytruda (pembrolizumab) compared to many other cancer treatments, with an incidence of approximately 2.7% for monotherapy and up to 6.6% when used in combination therapy. 1

Incidence and Risk Factors

• PD-1 inhibitors vs. PD-L1 inhibitors: PD-1 inhibitors like pembrolizumab have a higher incidence of pneumonitis (3.6%) compared to PD-L1 inhibitors (1.3%) 1
• Monotherapy vs. combination therapy:
  • Monotherapy: ~2.7% overall incidence 1
  • Combination with CTLA-4 inhibitors: ~6.6% (up to 3 times higher risk) 1
• Timing of onset: Median time to pneumonitis onset is 2.8 months, but can range from 9 days to 19.2 months 1
• Cancer type differences:
  • Similar incidence in melanoma and NSCLC (approximately 4-5%) 1
  • Earlier onset in NSCLC (median 2.1 months) vs. melanoma (median 5.2 months) 1
• Geographic differences: Japanese patients show higher incidence of pneumonitis with immune checkpoint inhibitors 1

Clinical Presentation and Diagnosis

Symptoms

• New or worsening shortness of breath
• Cough (new or worsening)
• Chest pain
• Reduced exercise tolerance
• Fatigue with activities of daily living
• Fever
• New or increasing oxygen requirements 1

Radiographic Findings

• Ground glass opacities
• Cryptogenic organizing pneumonia-like appearance
• Interstitial pneumonia pattern
• Hypersensitivity pneumonitis features 1

Diagnostic Approach

1. CT scan for any patient with respiratory symptoms on Keytruda
2. Rule out infection, disease progression, and other causes
3. Lung biopsy generally not required unless diagnosis is unclear 1

Management Based on Severity

Grade 1 (Asymptomatic, radiographic findings only)

• Consider holding Keytruda
• Monitor symptoms every 2-3 days
• Repeat chest CT prior to next scheduled dose 1

Grade 2 (Symptomatic, mild to moderate)

• Hold Keytruda
• Start corticosteroids (prednisone 1-2 mg/kg/day)
• If no improvement within 48-72 hours, treat as Grade 3 1

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

• Permanently discontinue Keytruda
• Hospitalize patient
• High-dose corticosteroids (methylprednisolone 1-2 mg/kg/day IV)
• If no improvement within 48 hours, consider additional immunosuppression (infliximab, mycophenolate mofetil, or IVIG) 1

Important Clinical Considerations

• Late-onset pneumonitis: Can occur even after discontinuation of Keytruda, with cases reported up to 7 months after the final dose 2
• Recurrence risk: Pneumonitis can recur when steroids are tapered too quickly 3
• Mortality risk: Pneumonitis is one of the most common causes of immune checkpoint inhibitor-related death 1
• Concurrent conditions: Other immune-related adverse events may occur simultaneously with pneumonitis in up to 50% of patients 1
• Pre-existing lung disease: Makes diagnosis more challenging and may increase risk 1

Clinical Pitfalls to Avoid

1. Delayed recognition: Any new respiratory symptom should prompt immediate evaluation 1
2. Inadequate steroid duration: Tapering steroids too quickly can lead to recurrence 3
3. Missing concurrent infections: Bacterial pneumonia can co-exist with immune-related pneumonitis 4
4. Overlooking late-onset pneumonitis: Vigilance should continue even after discontinuation of therapy 2
5. Insufficient monitoring: Regular follow-up imaging is necessary to confirm resolution 1

Careful monitoring, early recognition, and prompt treatment are essential for managing this potentially serious adverse effect of Keytruda therapy.