Pembrolizumab is a programmed cell death protein 1 (PD-1) inhibitor used in various cancers. Immune-related adverse events (irAEs) are common. Which irAE is most immediately life-threatening and requires immediate high-dose corticosteroid therapy?

• A Immune-related colitis (diarrhoea grade 2)
• B Immune-related hypothyroidism requiring levothyroxine
• C Immune-related vitiligo
• D Immune-related pneumonitis causing hypoxia and respiratory failure ✓

Explanation

Immune-related pneumonitis (irP) is the most immediately life-threatening irAE of checkpoint inhibitors; it can progress rapidly to respiratory failure and death. Patients with grade 3–4 pneumonitis (significant hypoxia, extensive infiltrates) require immediate hospitalisation, withholding of immunotherapy, and high-dose systemic corticosteroids (prednisolone 1–2 mg/kg/day). Severe colitis and myocarditis are also high-risk, but respiratory failure from pneumonitis has among the highest acute mortality of irAEs. Hypothyroidism and vitiligo are mild and managed conservatively.

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

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