Table 1.
Immune-related adverse effects (irAEs) in various organ systems associated with ipilimumab treatment.
| irAE | Overall Incidence (27) | Incidence of irAEs ≥ grade 3 (27) | Onset | Basic mechanism or associated findings | Treatment in addition to discontinuation of ipilimumab |
|---|---|---|---|---|---|
| Dermatologic effects (primarily involving a maculopapular rash) | 65% | < 3% | 2-3 weeks (28) | • Perivascular lymphocytic infiltrate into the epidermis (24, 25). • Melan-A-specific CD8+ T cells into the dermis (24, 30). • Sarcoidosis-type skin reaction (34-38). • Vitiligo (31, 32). |
Topical corticosteroids with antipruritic agents. Systemic corticosteroids if necessary. |
| Colitis/diarrhea | 33% | 10% | 6-7 weeks (28) | • Altered antibodies to enteric flora, T cell infiltration, and increased calprotectin (47). • Depletion of Tregs (48). • Perforation of the gastrointestinal tract is rare (45, 46). |
Systemic corticosteroids. Infliximab if necessary (48). Ocular evaluation (25). |
| Endocrine effects (hypophysitis, thyroiditis and adrenalitis) | < 5% | < 3% | 6-9 weeks (28) | • Enlarged pituitary causes a mass effect and hormone deficiencies. • Hypophysitis may be due to a type 2 hypersensitivity reaction (52). • Thyroiditis and hypothyroidism (63). • Graves’ disease (hyperthyroidism) (69). • Adrenalitis (65). |
Systemic corticosteroids. Hormone replacement therapy if necessary. |
| Hepatotoxicity | <2% | 1% | 6-7 weeks (28) | Damage to the hepatocytes or to the bile ducts occurs (67). | Systemic corticosteroids. |
| Ocular effects | 1.3% | 0.4% | variable | Graves’ ophthalmopathy (69,70); orbital inflammatory syndrome (71); optic neuropathy (72); and conjunctivitis, scleritis, and uveitis (25). | Corticosteroid eye drops and/or systemic corticosteroids (73). |
| Renal effects | 6 reported cases (77) | NA | variable | • Acute granulomatous tubulointerstitial nephritis (77). • Lupus nephritis (77). |
Systemic corticosteroids. |
| Neurologic effects | 0.1% | None | variable | Guillian-Barré syndrome (80); meningo-radiculo-nevritis (81); cerebral edema (82); aseptic meningitis (26); temporal arteritis (68); posterior reversible encephalopathy syndrome (83); peripheral neuropathy (84); Tolosa-Hunt syndrome (21); enteric neuropathy (85, 86); Multiple Sclerosis exacerbations (87); and chronic inflammatory demyelinating polyneuropathy (CIDP), transverse myelitis (TM), and myasthenia gravis–type syndrome (88). | Systemic corticosteroids. Possibly plasmapheresis, or intravenous immunoglobulin (IVIG). |
Note: Numbers in the parentheses show the reference number for individual studies and/or findings.