Immune-Mediated Adverse Events Associated with Ipilimumab CTLA-4 Blockade Therapy: The Underlying Mechanisms and Clinical Management

Table 1

Ipilimumab efficacy in phase II and III trials [16–21].

Study	Phase	Population (𝑛)	Treatment	ORR (%)	PFS	Median OS, months (95% CI)
CA184-022 [18]	II	Pretreated; (𝑛 = 217)	Ipi 10 mg/kg; Ipi 3 mg/kg; Ipi 0.3 mg/kg	11.1%; 4.2%; 0.0%	24-week: 18.9%; 24-week: 12.9%; 24-week: 2.7%	11.4 (6.9–16.1); 8.7 (6.9–12.1); 8.6 (7.7–12.7)
CA184-008 [22]	II	Heavily pretreated, progressed on prior therapy (𝑛 = 155)	Ipi 10 mg/kg	5.8%	NR	10.2 (7.6–16.3)
CA184-007 [23]	II	Treatment naïve and previously treated (𝑛 = 115)	Ipi 10 mg/kg; Ipi 10 mg/kg + budesonide^†	15.8%; 12.1%	NR	19.3 (12.0–34.5); 17.7 (6.8–45.0)
MDX010-08 [10]	II	Treatment naïve (𝑛 = 72)	Ipi 3 mg/kg*; Ipi 3 mg/kg* + DTIC	5.4%; 14.3%	NR	14.3 (10.2–18.8); 11.4 (6.1–15.6)
MDX010-20 [16]	III	Pretreated, progressed on prior therapy (𝑛 = 676)	Ipi 3 mg/kg + gp100; Ipi 3 mg/kg; Gp100	5.7%; 10.9%; 1.5%	Median: 2.76 months; Median: 2.86 months; Median: 2.76 months	10.0; 10.1; 6.4
CA184-024 [17]	III	Treatment naïve (𝑛 = 502)	Ipi 10 mg/kg + DTIC; DTIC	15.2%; 10.3%	Median PFS similar in both arms, but overall 24% reduction in risk of progression for ipi + DTIC versus DTIC; (HR 0.76; 𝑃 = 0.006)	11.2 (9.4–13.6); 9.1 (7.8–10.5)

∗Once every 4 weeks × 4 cycles (induction).
^†Prophylactic budesonide was added to determine if the rate of grade ≥2 diarrhea was reduced.
CI: confidence interval; DTIC: dacarbazine; HR: hazard ratio; NR: not reported; ORR: objective response rate; PFS: progression-free survival; OS: overall survival; WHO: World Health Organization.