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irAE Rechallenge Multi-organ — SCE Medical Oncology MCQ

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HardLung CancerirAE Rechallenge Multi-organSCE Medical Oncology

A patient receiving pembrolizumab develops immune-mediated hepatitis with ALT 8 times the upper limit of normal and normal baseline liver tests. Other causes are excluded, and corticosteroids return ALT to grade 1. Hypothyroidism remains controlled on levothyroxine. What should happen to pembrolizumab?

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Correct answer: B — Stop pembrolizumab permanently after this grade-three immune hepatitis episode

ALT eight times ULN is grade-three immune hepatitis, for which pembrolizumab should be permanently discontinued after other causes are excluded. Resume pembrolizumab after ALT returns to grade one and steroid taper completes: the current product guidance requires permanent discontinuation after grade-three hepatitis. Resume pembrolizumab at a reduced dose after ALT returns to grade one: checkpoint antibodies are not dose-reduced to mitigate immune hepatitis risk. Substitute nivolumab after ALT returns to grade one and steroid taper completes: switching within PD-1 blockade does not remove class recurrence risk. Continue pembrolizumab with mycophenolate after ALT returns to grade one: maintenance immunosuppression is not a route to continue treatment after this grade of toxicity.

Reference: KEYTRUDA 25 mg/mL UK summary of product characteristics (Current UK SmPC, updated June 2026): https://www.medicines.org.uk/emc/product/2498/smpc