What are the side effects of ipilimumab (Yervoy)?

Side Effects of Ipilimumab (Yervoy)

Ipilimumab causes immune-related adverse events (irAEs) in 60-85% of patients, with 10-27% developing severe grade 3-4 toxicities and approximately 2% experiencing potentially fatal reactions. 1

Common Side Effects

Ipilimumab's mechanism of action involves blocking CTLA-4, which removes inhibition of T-cell activation and releases the "brake" on immune responses. This immune system activation can lead to various side effects:

Most Common Side Effects (≥20%)

• Fatigue
• Diarrhea
• Pruritus (itching)
• Rash
• Nausea
• Headache 2

Immune-Related Adverse Events (irAEs)

Ipilimumab can cause immune-mediated inflammation in various organ systems:

Gastrointestinal

• Colitis/diarrhea (most common serious irAE)
• Abdominal pain 3, 1

Dermatologic

• Rash (often first to appear, within 8-12 weeks)
• Pruritus
• Dermatitis 3, 1

Hepatic

• Immune-mediated hepatitis
• Elevated liver enzymes 3, 2

Endocrine

• Hypophysitis (pituitary inflammation)
• Thyroiditis
• Adrenal insufficiency
• Hypothyroidism 3, 1, 4

Pulmonary

• Pneumonitis 3, 2

Neurological

• Various neurological disorders (rare but serious) 3, 1

Cardiovascular

• Myocarditis (rare but potentially fatal) 1

Renal

• Nephritis with renal dysfunction 2

Hematologic

• Anemia
• Leukopenia/neutropenia (rare but serious) 5

Other

• Infusion-related reactions 2

Severity and Dose-Dependency

The severity of side effects is dose-dependent:

• 10-27% develop grade 3-4 toxicities at 3 mg/kg
• 41.6% develop grade 3-4 toxicities at 10 mg/kg
• No grade 3-4 AEs observed at 0.3 mg/kg 3

Risk Factors

• Patients with underlying autoimmune disorders may be especially susceptible to serious immune-related reactions 1
• Men appear more prone to developing ipilimumab-induced hypophysitis than women 4

Timing of Side Effects

• Skin toxicities often develop first, typically within the first 8-12 weeks of treatment 3, 1
• Other irAEs can occur at any time during treatment or even after discontinuation 2

Management Considerations

• Early recognition is critical for effective management of irAEs
• Corticosteroids are the mainstay of treatment for most moderate to severe irAEs
• Severe cases may require:
  • High-dose parenteral pulsed methylprednisolone for hepatitis
  • Infliximab for corticosteroid-refractory colitis 6
• Most patients who develop hypophysitis remain on glucocorticoid replacement long-term 4

Monitoring Requirements

The FDA approval of ipilimumab included a Risk Evaluation and Mitigation Strategy (REMS) due to potential toxicity. Patients should be monitored with:

• Thyroid function studies
• Complete blood counts
• Liver function tests
• Metabolic panels
• Serum LDH tests 3, 1

Vigilant monitoring is essential as irAEs can affect any organ system and may occur even after treatment discontinuation.