Ipilimumab differs from nivolumab and pembrolizumab in its checkpoint target and adverse event pattern. The distinguishing feature of ipilimumab is:

• A It blocks PD-L1 and uniquely spares the gastrointestinal tract
• B It blocks CTLA-4 and characteristically causes isolated hypothyroidism without colitis
• C It blocks CTLA-4 and causes severe diarrhoea and colitis at a higher rate than anti-PD-1 agents ✓
• D It blocks LAG-3 and causes adrenal insufficiency as its dominant toxicity

Explanation

Ipilimumab is a fully human anti-CTLA-4 antibody acting at the priming phase of T-cell activation in lymph nodes. CTLA-4 blockade produces more frequent and more severe immune-related enterocolitis than PD-1 inhibition, with grade 3 to 4 diarrhoea occurring in roughly 10 percent of treated patients, and it carries higher overall treatment-related mortality than anti-PD-1 monotherapy. Anti-PD-1 agents more typically cause pneumonitis, thyroid dysfunction and vitiligo-like depigmentation, while PD-L1 and LAG-3 blockers are different drug classes entirely.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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