Table 2: Frequency of specific AEs* and irAEs in a pooled analysis of 1498 patients in phase I–III studies of ipilimumab in unresectable stage III or stage IV melanoma [24].

AEs ( = 1498)Any grade, (%)Grade 3-4, (%)Grade 5, (%)

Specific AE
 Diarrhea 554 (37.0)104 (6.9)0 (0)
 Colitis 120 (8.0)74 (4.9)1 (<0.1)
 Enterocolitis 18 (1.2)9 (0.6)0 (0)
 Large intestine perforation 4 (0.3)3 (0.2)1 (<0.1)
 Intestinal perforation 3 (0.2)2 (0.1)1 (<0.1)
 Rash 498 (33.2)37 (2.5)0 (0)
 Pruritus 413 (27.6)6 (0.4)0 (0)
 Abnormal hepatic function 74 (4.9)17 (1.1)1 (<0.1)
 Hepatitis 10 (0.7)10 (0.7)0 (0)
 Hepatic failure 7 (0.5)1 (<0.1)5 (0.3)
 Peripheral sensory neuropathy 67 (4.5)6 (0.4)0 (0)
 Neuropathy peripheral 13 (0.9)0 (0)0 (0)
 Peripheral motor neuropathy 9 (0.6)6 (0.4)0 (0)
 Hypopituitarism 40 (2.7)31 (2.1)0 (0)
 Hypothyroidism 27 (1.8)2 (0.1)0 (0)
 Adrenal insufficiency 11 (0.7)5 (0.3)0 (0)
irAEs grouped by organ class
 Any irAE962 (64.2) 266 (17.8)9 (0.6)
 Dermatologic 672 (44.9)39 (2.6)0 (0)
 Gastrointestinal487 (32.5)137 (9.1)3 (0.2)
 Endocrine 68 (4.5)34 (2.3)0 (0)
 Hepatic 24 (1.6)16 (1.1)2 (0.1)
 Ocular 20 (1.3)6 (0.4)0 (0)
 Neurologic 2 (0.1)0 (0)1 (<0.1)
 Cardiovascular (myocarditis)2 (0.1)2 (0.1)0 (0)

Regardless of causality. Subjects may have had more than one event. Unknown intensities are included in “Any Grade” column. Grade 5 = death. Results from the following trials were included in the analysis: MDX010-02, -15, -03, -04, -13, -05, -19, -08, -20; CA184-042, -004, -008, -022, -007: These trials ranged from phase I–III, investigated ipilimumab at various doses (0.1–20 mg/kg), as monotherapy or in combination with various agents. All patients included had unresectable stage III or IV melanoma, no prior history or clinical evidence of autoimmune disease or treatment with immunosuppressive drugs, and received at least one dose of ipilimumab. Patient characteristics such as age, prior treatment history and performance status varied among trials. Safety events included in this analysis were those reported between first dose and 70 days after last dose of study therapy.