Late Onset Ipilimumab-Induced Pericarditis and Pericardial Effusion: A Rare but Life Threatening Complication

Table 2

Ipilimumab induced immune related adverse events in Phases II and III trials.

Study	Pathology	Stage	Range of median Age	Pt. No.	Treatments	Overall survival rate			Grade 3/4 immune related adverse events rate
						Ipilimumab (1)	Ipilimumab (2)	Ctrl	Ipilimumab (1)	Ipilimumab (2)	Ctrl
Robert et al., 2011 [9]	Cutaneous melanoma	III; IV	56.4–57.5	502	Ipilimumab (10 mg/kg) + dacarbazine (1) versus placebo + dacarbazine	47.3% (1 yr); 28.5% (2 yr); 20.8% (3 yr)		36.3% (1 yr); 17.9% (2 yr); 12.2% (3 yr)	Any events: 41.7%; dermatologic: 3.2%; GI: 5.6%; hepatic: 30%		Any events: 6.0%; dermatologic: 0%; GI: 0%; hepatic: 1.2%
Hodi et al., 2010 [8]	LHA-A^*0201 (+) cutaneous melanoma	III; IV	55.6–57.4	676	Ipilimumab (3 mg/kg) + gp100 (1) versus ipilimumab (3 mg/kg) (2) versus gp100	43.6% (1 yr); 21.6% (2 yr)	45.6% (1 yr); 23.5% (2 yr)	25.3% (1 yr); 13.7% (2 yr)	Any events: 10.2%; dermatologic: 2.4%; GI: 5.8%; hepatic: 3.2%; endocrine: 1.1%; others: 1.3%	Any events: 14.5%; dermatologic: 1.5%; GI: 7.6%; hepatic: 0%; endocrine: 3.8%; others: 2.3%	Any events: 3.0%; dermatologic: 0%; GI: 0.8%; hepatic: 2.3%; endocrine: 0%; others: 3.1%
Wolchok et al., 2010 [11]	Cutaneous melanoma	III; IV	56–59	217	Ipilimumab (10 mg/kg) (1) versus ipilimumab (3 mg/kg) (2)	48.6% (1 yr); 29.8% (2 yr)	39.6% (1 yr); 24.2% (2 yr)		Any events: 25.4%; dermatologic: 4.2%; GI: 15.5%; hepatic: 3.0%; endocrine: 1.4%; others: 2.8%	Any events: 7.0%; dermatologic: 1.4%; GI: 2.8%; hepatic: 0%; endocrine: 2.8%; others: 0%
Hersh et al., 2011 [13]	Cutaneous melanoma	III; IV	60–66	76	Ipilimumab (3 mg/kg) + dacarbazine (1) versus ipilimumab (3 mg/kg) (2)	62.0% (1 yr); 24.0% (2 yr); 20.0% (3 yr)	45.0% (1 yr); 21.0% (2 yr); 9.0% (3 yr)		Any events: 17.1%; dermatologic: 42.9%; GI: 28.6%	Any events: 7.1%; dermatologic: 48.7%; GI: 20.5%
Weber et al., 2009 [12]	Cutaneous melanoma	III; IV	58–61	115	Ipilimumab (10 mg/kg) + placebo (1) versus ipilimumab (10 mg/kg) + budesonide (2)	62.4% (1 yr); 41.7% (2 yr)	55.9% (1 yr); 40.5% (2 yr)		Any events: 38.0%; dermatologic: 0%; GI: 23.0%; hepatic: 12.0%; endocrine: 5.0%; others: 2.0%	Any events: 41.0%; dermatologic: 5.0%; GI: 24.0%; hepatic: 9.0%; endocrine: 5.0%; others: 2.0%

The immune-related adverse events were prospectively defined (medical dictionary for regulatory activities, version 13.0).
The immune-related adverse events were defined as an adverse event that was associated with exposure to the study drug and that was consistent with an immune phenomenon.
The adverse events were graded by the National Cancer Institute’s common terminology criteria for adverse events version 3.0.
Other immune related adverse events included scleritis () and pneumonitis ().
Immune related adverse events were coded according to the Medical Dictionary for Regulatory Affairs, and severities were graded using Common Toxicity Criteria version 2.0. Dermatologic and GI adverse events included grade ≥1 in this study.