Immune Toxicity with Checkpoint Inhibition for Metastatic Melanoma: Case Series and Clinical Management
Table 3
Gastrointestinal and hepatic irAE: management algorithm.
(a)
Gastrointestinal irAE
Investigations
Management
Grade 1/mild
Diarrhoea (<4 stools/day over baseline)
Stool MCS
Continue checkpoint inhibitor monotherapy (If on dual checkpoint inhibitor therapy, patient will need careful consideration and monitoring closely) Antimotility agents, for example, loperamide Fluid replacement If prolonged symptoms, treat as Grade 2
Grade 2/moderate
Diarrhoea (4–6 stools/day over baseline) Colitis (pain, mucus, or blood)
Stool MCS Consider colonoscopy
Delay immunotherapy until resolving to Grade ≤ 1 (If on dual checkpoint inhibitor therapy, consider ceasing anti-CTLA-4) Consider hospital admission Gastroenterology referral Oral prednisolone 1 mg/kg/day for colitis or persistent diarrhoea
Grade 3-4/severe/life-threatening
Diarrhoea (≥7 stools/day over baseline, incontinence, life-threatening) Colitis (severe pain, blood, mucus, and peritonism)
Stools MCS Colonoscopy, if colitis suspected or persistent diarrhoea despite steroids AXR/CT if suspected perforation
Grade 3 toxicity: Delay anti-PD-1 until resolving to Grade ≤ 1 with careful consideration as to retreatment Cease anti-CTLA-4 Grade 4 toxicity (life-threatening, perforation): Discontinue immunotherapy permanently Hospital admission Gastroenterology referral Pulse with methylprednisolone 1-2 mg/kg/day If no response to steroid therapy (3–5 days), consider infliximab 5 mg/kg (if no perforation/sepsis)
LFTs and viral serology Monitor LFTs weekly Exclude disease progression or medication-related causes
Continue checkpoint inhibitor therapy
Grade 2/moderate
Hepatic (AST/ALT >3–≤5x ULN and/or total bilirubin >1.5–≤3x ULN)
LFTs and viral serology Exclude disease progression or medication-related causes LFTs every 3 days
Delay checkpoint inhibitor therapy until improving to baseline Consider gastroenterology referral Consider oral prednisolone 1 mg/kg/day with slow taper
Grade 3-4/severe/life-threatening
Hepatic (AST/ALT >5x ULN and/or total bilirubin >3x ULN)
LFTs and viral serology Exclude disease progression or medication-related causes LFTs daily
Discontinue checkpoint inhibitor therapy Hospital admission Gastroenterology referral Pulse with methylprednisolone 1-2 mg/kg/day for 3 days Steroid refractory hepatitis: If no improvement after 3–5 days consider the following: Mycophenolate mofetil 500 mg–1 g bd and escalation of methylprednisolone to 15 mg/kg daily (maximum 1 gm/day) for 3 days
Switch to oral prednisolone 1 mg/kg/day with slow taper over 1 month or longer. PJP (e.g., bactrim DS 1/2 tablet daily) and GIT ulcer prophylaxis therapy when patients are on prolonged steroid taper. Monitor blood glucose.
