Table 1.
Most frequently reported immune-related adverse events with the combination of ipililumab/nivolumab or either agent alone among melanoma patients enrolled in the CheckMate-067 trial.
| Combination ICI | Anti-PD1 | Anti-CTLA4 | Clinical Features | ||||
|---|---|---|---|---|---|---|---|
| Any Grade | Grade 3–4 | Any Grade | Grade 3–4 | Any Grade | Grade 3–4 | ||
| Cutaneous | 62% | 6% | 46% | 2% | 56% | 3% | Morbilliform eruption can be seen with ipilimumab, skin manifestations less severe with anti-PD1 |
| Rash/Pruritis | 53% | 6% | 37% | 2% | 51% | 3% | |
| Vitiligo | 9% | 0 | 9% | <1% | 5% | 0 | |
| Gastrointestinal | 48% | 15% | 22% | 4% | 38% | 12% | Diarrhea in almost all patients with colitis (92%); abdominal pain, nausea/vomiting |
| Colitis | 13% | 8% | 2% | 1% | 11% | 8% | |
| Diarrhea | 45% | 9% | 21% | 3% | 34% | 6% | |
| Endocrine | 34% | 6% | 17% | 2% | 12% | 3% | |
| Hypothyroidism | 17% | <1% | 11% | 0% | 5% | 0% | Hyperthyroidism is usually transient and followed by permanent hypothyroidism |
| Hyperthyroidism | 11% | 1% | 4% | 0% | 1% | 0% | |
| Hypophysitis | 7% | 2% | 1% | <1% | 4% | 2% | Hypophysitis presents with fatigue, headache, weakness, characteristic findings noted on MRI; can result in multiple hormone deficiencies; adrenal insufficiency generally permanent |
| Adrenal Insufficiency | 4% | 2% | 1% | 1% | 1% | <1% | |
| Hepatoxicity | 33% | 20% | 8% | 3% | 7% | 2% | Predominantly asymptomatic elevations in transaminases; rare severe auto-immune like hepatitis and liver failure |
| Pneumonitis | 7% | 1% | 2% | <1% | 2% | <1% | Dyspnea and cough most common symptoms but variable clinical and radiographic presentation |