CTLA-4 Inhibitor Pregnancy: Contraindicated — immune checkpoint inhibition disrupts fetal tolerance; effective contraception during and for 3 months after treatment

Ipilimumab (RCC — in Combination)

Brand names: Yervoy

Adult dose

Dose: 1 mg/kg IV every 3 weeks for 4 doses (in combination with nivolumab 3 mg/kg); standalone urothelial: 3 mg/kg every 3 weeks ×4 (different regimen)

Route: Intravenous infusion over 30 minutes

Frequency: Every 3 weeks ×4 cycles (induction), then nivolumab monotherapy maintenance

Max: 3 mg/kg per dose (depending on regimen)

Used in combination with nivolumab for first-line intermediate/poor-risk mRCC (CheckMate 214); lower dose (1 mg/kg) reduces irAE rate vs melanoma dose (3 mg/kg) while maintaining efficacy

Paediatric dose

Dose: Not established for urology N/A/kg

Route: N/A

Frequency: N/A

Max: N/A

Not licensed for GU malignancies in paediatrics

Dose adjustments

Renal

No dose adjustment required

Hepatic

Withhold for grade 2 hepatitis; permanently discontinue for grade 3-4

Paediatric weight-based calculator

Patient weight (kg)

Not licensed for GU malignancies in paediatrics

Clinical pearls

CheckMate 214 dual checkpoint blockade rationale: CTLA-4 inhibition (ipilimumab) promotes T-cell priming and expands the T-cell repertoire; PD-1 inhibition (nivolumab) prevents T-cell exhaustion at the tumour site — complementary mechanisms produce synergistic anti-tumour immunity with durable responses
Hypophysitis: CTLA-4-specific irAE — presents with headache, fatigue, visual field defects, hyponatraemia; MRI pituitary shows gland enlargement; cortisol and pituitary hormone panel required; usually requires lifelong hormone replacement (cortisol ± T4 ± testosterone); do not delay diagnosis
Dose reduction in urology vs melanoma: ipilimumab 1 mg/kg (not 3 mg/kg as in melanoma) in CheckMate 214 combination — reduces severe irAE rate from ~35% to ~22% while maintaining OS benefit; clinically important to prescribe correct dose for indication
Steroid-refractory colitis: infliximab 5 mg/kg IV is the established rescue — anti-TNF therapy; give promptly if colitis fails to respond to 3-5 days of IV methylprednisolone 1-2 mg/kg; vedolizumab is an alternative; delay risks bowel perforation
Long-term data: 7-year follow-up of CheckMate 214 shows sustained benefit with estimated 42% alive at 7 years in nivolumab+ipilimumab arm vs 26% sunitinib — supports dual checkpoint blockade as the treatment producing most durable remissions

Contraindications

Active severe autoimmune disease
Known hypersensitivity to ipilimumab

Side effects

Immune colitis (most common severe irAE — diarrhoea)
Immune hepatitis
Hypophysitis (CTLA-4 specific — headache, visual changes)
Adrenal insufficiency
Rash
Elevated LFTs
Higher irAE burden than PD-1 monotherapy

Interactions

Corticosteroids — immunosuppressive doses reduce efficacy; use only for irAE management
Live vaccines — avoid

Monitoring

LFTs (before each dose — hepatitis)
FBC and cortisol (pituitary/adrenal function)
TFTs
GI symptoms diary
Pituitary MRI if headache/visual change
Glucose (diabetes irAE)

Reference: BNFc; BNF 90; CheckMate 214 (Motzer et al. NEJM 2018); 7-year OS data (Motzer et al. NEJM 2022); NICE TA581; MHRA SPC Yervoy; EAU RCC Guidelines 2024. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways