Ipilimumab
Trade name: Yervoy.
Ipilimumab is a fully human anti-CTLA-4 monoclonal antibody. CTLA-4 acts upstream of PD-1 to limit T-cell activation. CTLA-4 blockade is more potent but more toxic than PD-1 blockade. Now used predominantly in combination with nivolumab as first-line metastatic melanoma therapy — combination ICI delivers the longest median overall survival but with substantial grade 3–4 irAE rates.
Indications (UK)
- Metastatic melanoma — first-line in combination with nivolumab: NICE TA400. The dual ICI combination delivers the longest median overall survival across the contemporary melanoma trials, at the cost of higher grade 3–4 irAE rates than anti-PD-1 monotherapy.
- Ipilimumab monotherapy: NICE TA319 (2014), for previously untreated advanced unresectable / metastatic melanoma. Largely superseded by combination ipi + nivo or anti-PD-1 monotherapy; retained for use where combination ICI is contraindicated.
- Adjuvant ipilimumab is not NHS-commissioned in the UK; CheckMate-915 did not show benefit for adjuvant ipi + nivo over nivo monotherapy.
Dosing
- Combined induction: ipilimumab 3 mg/kg + nivolumab 1 mg/kg IV every 3 weeks ×4 doses.
- Followed by nivolumab maintenance.
- Monotherapy historic dose: 3 mg/kg every 3 weeks ×4 doses.
irAEs
Ipilimumab has a higher and earlier irAE rate than anti-PD-1. Combination ipilimumab + nivolumab grade 3–4 irAE rate is approximately 60% vs 20% for nivolumab monotherapy. Hypophysitis is more characteristic of CTLA-4 blockade. See irAE management principles.
Centres delivering ipilimumab + nivolumab must have rapid steroid availability, robust 24-hour irAE pathways, and patient education protocols. Many irAEs occur within the first 12 weeks; some present months after the last dose.
References
- Larkin J et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med; 2019.
- Postow MA et al. Nivolumab and ipilimumab versus ipilimumab alone in untreated melanoma. N Engl J Med; 2015.
- NICE TA400. Nivolumab in combination with ipilimumab for treating advanced melanoma. London: NICE; 2016. NICE TA319. Ipilimumab for previously untreated advanced (unresectable or metastatic) melanoma. London: NICE; 2014.
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