What is the recommended treatment for pneumonitis (inflammation of the lungs) associated with pembrolizumab (generic name: pembrolizumab), with symptoms of shortness of breath and cough, elevated C-reactive protein (CRP) levels, and normal oxygen saturation levels?

Management of Pembrolizumab-Induced Pneumonitis with Normal Oxygen Saturation

For pembrolizumab-induced pneumonitis with normal oxygen saturation but shortness of breath, cough, and elevated CRP, high-dose corticosteroids (prednisone 1-2 mg/kg/day or equivalent) should be initiated immediately while temporarily holding pembrolizumab. 1

Grading and Assessment

Pneumonitis severity should be assessed based on clinical presentation:

• Grade 1: Asymptomatic, radiographic findings only
• Grade 2: Symptomatic (like your patient with shortness of breath and cough), but not interfering with activities of daily living
• Grade 3: Severe symptoms limiting self-care activities
• Grade 4: Life-threatening respiratory compromise

Your patient presents with:

• Shortness of breath and cough (symptomatic)
• Normal oxygen saturation
• Elevated CRP (indicating inflammation)
• This likely represents Grade 2 pneumonitis

Treatment Algorithm

For Grade 2 Pneumonitis (Your Patient):

1. Hold pembrolizumab immediately

2. Initiate oral prednisone 1-2 mg/kg/day (or equivalent)

3. Consider empiric antibiotics to cover potential concurrent bacterial infection (especially with elevated CRP)

4. Monitor closely with:

   • Daily assessment of symptoms
   • Oxygen saturation monitoring
   • Consider repeat CRP in 48-72 hours to track inflammatory response
   • Chest imaging in 1-2 weeks to assess response

5. Steroid taper:

   • Continue high-dose steroids until symptoms improve
   • Then taper slowly over at least 4-6 weeks
   • Rapid tapering can lead to recurrence 2, 3

If Improvement Occurs:

• Complete the full steroid taper
• Consider resuming pembrolizumab at a reduced dose only after complete resolution of pneumonitis and after discussion with oncology team

If No Improvement Within 48-72 Hours or Worsening:

• Upgrade to Grade 3 management
• Hospitalize if not already admitted
• Switch to IV methylprednisolone 2-4 mg/kg/day
• Consider additional immunosuppression with infliximab (5 mg/kg) 4
• Obtain pulmonology consultation
• Consider bronchoscopy with bronchoalveolar lavage to rule out infection

Special Considerations

1. Infection risk:

   • Elevated CRP may indicate concurrent bacterial infection
   • Consider empiric antibiotics while awaiting cultures
   • Procalcitonin testing may help differentiate between pure pneumonitis and superimposed bacterial pneumonia 5

2. Monitoring:

   • Despite normal oxygen saturation now, pneumonitis can rapidly progress 6
   • Daily monitoring of symptoms and oxygen saturation is essential
   • Any decline in oxygen saturation warrants immediate escalation of care

3. Recurrence risk:

   • Pneumonitis can recur with rapid steroid tapering
   • Ensure slow, gradual taper over 4-6 weeks minimum
   • Some patients may require prolonged steroid courses

4. Mortality risk:

   • Pneumonitis with superimposed bacterial infection carries higher mortality 5
   • Early aggressive management is critical to prevent progression to respiratory failure

Pitfalls to Avoid

1. Delaying steroid initiation while waiting for infectious workup
2. Tapering steroids too quickly, which can lead to recurrence
3. Missing concurrent bacterial pneumonia (consider empiric antibiotics)
4. Restarting pembrolizumab too soon before complete resolution
5. Underestimating severity due to normal oxygen saturation (pneumonitis can rapidly progress)

Remember that pneumonitis is a potentially fatal complication of pembrolizumab therapy, and early aggressive management is essential for optimal outcomes.