Can pembrolizumab (pembrolizumab) be continued after grade 1-2 pneumonitis has been treated?

Management of Pembrolizumab After Treated Grade 1-2 Pneumonitis

Pembrolizumab can be cautiously resumed after successful treatment of grade 1-2 pneumonitis, with close monitoring for recurrence. 1

Understanding Immune Checkpoint Inhibitor Pneumonitis

Immune checkpoint inhibitor (ICI) pneumonitis is a potentially serious immune-related adverse event (irAE) with the following characteristics:

• Incidence with PD-1 inhibitors like pembrolizumab: 2.7% for all grades, 0.8% for grade 3 or higher 1
• Higher risk in patients with:
  • History of asthma or COPD (5.3%)
  • Prior thoracic radiation (6.0%)
  • Current or former smoking status 1
• Most common radiologic patterns: organizing pneumonia (23%), followed by hypersensitivity pneumonitis (16%) 1

Decision Algorithm for Resuming Pembrolizumab

For Grade 1 Pneumonitis (Asymptomatic, radiographic changes only):

1. Can continue pembrolizumab without dose adjustment at the treating physician's discretion 1
2. Patient education is critical - inform about warning signs that require immediate medical attention
3. Implement more frequent monitoring with chest imaging

For Grade 2 Pneumonitis (Symptomatic, affecting ADLs):

1. Temporarily withhold pembrolizumab until symptoms resolve to Grade 0-1 2
2. Administer systemic corticosteroids (1-2 mg/kg/day prednisone or equivalent) 2
3. Taper corticosteroids slowly over at least 4-6 weeks to prevent recrudescence 3
4. Once symptoms resolve to Grade 0-1 and corticosteroid taper is complete, pembrolizumab can be cautiously resumed 2
5. Implement more frequent monitoring with pulmonary function tests and imaging

Contraindications to Resuming Pembrolizumab:

• Recurrent pneumonitis (Grade 3 or higher)
• Inability to reduce corticosteroid dose to ≤10 mg prednisone (or equivalent) within 12 weeks 2
• Progression to Grade 3-4 pneumonitis at any point 2

Monitoring After Resumption

1. More frequent clinical assessments for respiratory symptoms
2. Regular chest imaging (consider every 2-3 cycles initially)
3. Pulmonary function tests as clinically indicated
4. Patient education on early reporting of symptoms
5. Low threshold for bronchoscopy with bronchoalveolar lavage if symptoms recur 3

Important Caveats and Pitfalls

• Risk of recurrence: Studies show that approximately 23% of patients who resume pembrolizumab after pneumonitis may experience recurrence 2
• Late-onset pneumonitis: Pneumonitis can occur even months after discontinuation of pembrolizumab 4
• Infection risk: Always rule out infectious etiologies before attributing pulmonary symptoms to pneumonitis, especially in patients on corticosteroids 5, 6
• Consider prophylactic antibiotics in high-risk patients receiving corticosteroids for pneumonitis management 5
• Steroid-refractory cases: Consider additional immunosuppression with infliximab (5 mg/kg) if pneumonitis does not improve with corticosteroids within 48-72 hours 3, 7

Novel Approaches

For patients with a history of severe (Grade 3) pneumonitis who absolutely require pembrolizumab due to lack of alternatives, emerging case reports suggest that concurrent IL-6 blockade with tocilizumab may allow safe rechallenge 8. However, this approach should be considered experimental and used only in specialized centers with experience managing severe irAEs.

Remember that pneumonitis is the most common toxicity leading to PD-1/PD-L1-related mortality, accounting for 35% of all deaths related to these agents 1. Therefore, careful monitoring and prompt management are essential when resuming pembrolizumab after pneumonitis.