Ipilimumab — Drug Monograph
Brand names: Yervoy
Drug class: Checkpoint Inhibitor
Mechanism of Action
Human anti-CTLA-4 (cytotoxic T-lymphocyte-associated antigen-4) IgG1 monoclonal antibody. CTLA-4 is expressed on activated T cells and competes with CD28 for CD80/CD86 co-stimulatory ligands on antigen-presenting cells. CTLA-4 engagement provides an inhibitory signal, dampening early T-cell activation. Ipilimumab blocks this inhibitory checkpoint, enhancing T-cell priming and antitumor immune responses at the level of lymph nodes (earlier in the immune activation cascade than PD-1). The first checkpoint inhibitor FDA-approved (2011, melanoma).
FDA Indications
- Unresectable or metastatic melanoma (monotherapy or with nivolumab)
- Adjuvant treatment of cutaneous melanoma (with nodal involvement or metastatic disease, post-resection)
- MSI-H/dMMR metastatic colorectal cancer — first-line with nivolumab
- Hepatocellular carcinoma — second-line with nivolumab
- NSCLC — first-line with nivolumab and chemotherapy
- Malignant pleural mesothelioma — first-line with nivolumab
- Renal cell carcinoma — first-line with nivolumab
- Esophageal SCC — first-line with nivolumab
Common Side Effects
- Fatigue
- Diarrhea (most common; can be severe colitis)
- Rash, pruritus
- Nausea
- Decreased appetite
- Endocrinopathies (hypophysitis most characteristic)
Clinical Pearl
Hypophysitis (inflammation of the pituitary gland) is the signature irAE of ipilimumab — more common than with PD-1 inhibitors. Presentation: severe headache, visual field defects, fatigue, and features of pituitary hormone deficiencies (central hypothyroidism, adrenal insufficiency). MRI shows enlarged pituitary. Treatment: high-dose corticosteroids acutely, then hormone replacement (hydrocortisone and levothyroxine) which is often lifelong. Ipilimumab need not be discontinued for Grade 2…
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