Pembrolizumab, an anti-PD-1 checkpoint inhibitor, can cause immune-related adverse events (irAEs). A patient develops grade 3 immune-related hepatitis 8 weeks after starting pembrolizumab for NSCLC. The correct management is:

• A Continue pembrolizumab unchanged; transaminase rises self-resolve with acetylcysteine hepatoprotection
• B Switch to atezolizumab (anti-PD-L1) which has lower hepatotoxicity risk while continuing NSCLC treatment
• C Discontinue pembrolizumab permanently and start high-dose systemic corticosteroids (methylprednisolone 1–2 mg/kg/day); add mycophenolate mofetil if no response in 5–7 days ✓
• D Reduce pembrolizumab dose to 50% and add ursodeoxycholic acid for hepatoprotection

Explanation

Grade 3 immune-related hepatitis (ALT/AST >5× ULN) from checkpoint inhibitors requires: (1) Permanent discontinuation of pembrolizumab (grade 3 irAE); (2) High-dose corticosteroids (prednisolone 1–2 mg/kg/day or IV methylprednisolone if severe), tapered over at least 4 weeks; (3) If no response within 5–7 days, mycophenolate mofetil is added as a steroid-sparing immunosuppressant (Note: infliximab is contraindicated in checkpoint inhibitor hepatitis as it is itself hepatotoxic). Grade 1–2 hepatitis can be managed by holding pembrolizumab and monitoring. Switching to another checkpoint inhibitor does not prevent recurrence and is not standard practice.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.