What is the management of pembrolizumab (pembrolizumab, an anti-PD-1 antibody) induced pneumonia in a cancer patient with a compromised immune system?

Management of Pembrolizumab-Induced Pneumonitis

Immediately discontinue pembrolizumab and initiate corticosteroids at 1-2 mg/kg/day methylprednisolone IV (or prednisone equivalent orally) for grade 2 or higher pneumonitis. 1, 2

Immediate Actions Upon Suspicion

• Stop pembrolizumab immediately when pneumonitis is suspected at grade 2 or higher severity 3, 1
• Obtain chest CT scan urgently to identify the radiographic pattern (organizing pneumonia, hypersensitivity pneumonitis, NSIP, or diffuse alveolar damage patterns) 1, 2
• Exclude infectious causes through bronchoscopy with bronchoalveolar lavage, including bacterial cultures, viral PCR (particularly CMV in immunosuppressed patients), and fungal studies 1, 4, 5

Risk Stratification in Cancer Patients

Your patient faces elevated risk given their immunocompromised state. Specific high-risk factors include:

• Prior thoracic radiation: 6.0% pneumonitis incidence 1, 2
• Underlying lung disease (asthma/COPD): 5.3% incidence 1
• Lung cancer patients: Higher incidence (up to 6%) with earlier onset (median 2.1 months vs 5.2 months in melanoma) 1, 2
• Male sex and smoking history: Increased risk 2

Corticosteroid Dosing by Grade

Grade 2 (moderate symptoms, limiting instrumental ADLs):

• Prednisone 1 mg/kg/day orally 1
• Continue pembrolizumab hold 1

Grade 3-4 (severe symptoms, life-threatening):

• Methylprednisolone 1-2 mg/kg/day IV or prednisone equivalent 1
• Permanently discontinue pembrolizumab 1
• Consider ICU admission for grade 4 6, 5

Steroid Taper Protocol

• Minimum 4-week taper to prevent rebound inflammation 1
• Do not taper until clear radiographic and clinical improvement documented 1, 7
• Monitor for recurrence during taper, which can occur even months after cessation 7

Refractory Pneumonitis Management

If no improvement after 48 hours of high-dose corticosteroids:

• Add infliximab (anti-TNF therapy) or mycophenolate mofetil as second-line immunosuppression 1, 2
• Reassess for superimposed infection, particularly in deteriorating patients 4, 5

Critical Pitfalls in Immunocompromised Patients

Superimposed infections are the major cause of mortality:

• CMV pneumonia can complicate steroid-treated checkpoint inhibitor pneumonitis and carries high mortality despite antiviral therapy 4
• Bacterial pneumonia superimposed on pembrolizumab pneumonitis has poor prognosis; distinguish by elevated procalcitonin levels 5
• Influenza and other viral infections may trigger or worsen immune-related adverse events in these patients 8
• Maintain high suspicion and low threshold for bronchoscopy with comprehensive infectious workup in any patient not improving on steroids 4, 5

Prognosis and Outcomes

• Resolution rate with appropriate treatment: 59-77% 1
• Fatal pneumonitis occurs in 9% of severe cases and accounts for 35% of all PD-1/PD-L1-related deaths 1, 2
• Chronic pneumonitis develops in approximately 2% despite >3 months of corticosteroids 1
• Treatment-related deaths are more common in NSCLC patients 1

Rechallenge Considerations

Never rechallenge with pembrolizumab after grade 3-4 pneumonitis 2

• In documented cases, 2 of 7 patients re-treated developed recurrent pneumonitis 2
• Late-onset recurrent pneumonitis can occur >100 days after the last pembrolizumab dose 7
• For grade 2 pneumonitis that fully resolves, rechallenge carries significant risk and requires careful risk-benefit discussion 1

Radiographic Pattern and Severity Correlation

The CT pattern predicts severity:

• Diffuse alveolar damage (DAD): Highest grade, worst prognosis 1, 2
• Organizing pneumonia (OP): Most common pattern (23%), moderate severity 2
• Hypersensitivity pneumonitis (HP) and NSIP: Lower grade patterns 1, 2