Immune checkpoint inhibitors (PD-1/PD-L1 inhibitors) can cause immune-related adverse events (irAEs). A patient on pembrolizumab for melanoma develops new-onset severe diarrhoea (Grade 3, >7 stools/day above baseline). The CORRECT management is:

• A Continue pembrolizumab; treat with loperamide and dietary modification
• B Hold pembrolizumab; start high-dose IV methylprednisolone 1–2 mg/kg/day; perform flexible sigmoidoscopy; add infliximab 5 mg/kg if no improvement in 48–72 hours ✓
• C Permanently discontinue pembrolizumab; no steroids as they may worsen anti-tumour immunity
• D Reduce pembrolizumab dose by 50%; start oral budesonide

Explanation

Grade 3 immune-related colitis (>7 stools/day) from checkpoint inhibitors requires: holding (not necessarily permanently discontinuing) the immunotherapy; high-dose systemic corticosteroids (IV methylprednisolone 1–2 mg/kg/day per ASCO/ESMO guidelines); flexible sigmoidoscopy/colonoscopy to confirm diagnosis and exclude infection; and infliximab 5 mg/kg IV (or vedolizumab) if steroid-refractory within 48–72 hours. Grade 1–2 toxicity may be managed with antidiarrhoeals and observation; Grade 4 or steroid-refractory cases warrant permanent discontinuation. Checkpoint inhibitors should not be dose-reduced — they are either held or discontinued.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.