Table 3. Adverse Events in the Safety Population✫.
| Adverse Event | Ipilimumab plus gp100 (N = 380) | Ipilimumab Alone (N = 131) | gp100 Alone (N = 132) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Total | Grade 3 | Grade 4 | Total | Grade 3 | Grade 4 | Total | Grade 3 | Grade 4 | |
| number of patients (percent) | |||||||||
| Any event | 374 (98.4) | 147 (38.7) | 26 (6.8) | 127 (96.9) | 49 (37.4) | 11 (8.4) | 128 (97.0) | 54 (40.9) | 8 (6.1) |
| Any drug-related event | 338 (88.9) | 62 (16.3) | 4 (1.1) | 105 (80.2) | 25 (19.1) | 5 (3.8) | 104 (78.8) | 15 (11.4) | 0 |
| Gastrointestinal disorders | |||||||||
| Diarrhea | 146 (38.4) | 16 (4.2) | 1 (0.3) | 43 (32.8) | 7 (5.3) | 0 | 26 (19.7) | 1 (0.8) | 0 |
| Nausea | 129 (33.9) | 5 (1.3) | 1 (0.3) | 46 (35.1) | 3 (2.3) | 0 | 52 (39.4) | 3 (2.3) | 0 |
| Constipation | 81 (21.3) | 3 (0.8) | 0 | 27 (20.6) | 3 (2.3) | 0 | 34 (25.8) | 1 (0.8) | 0 |
| Vomiting | 75 (19.7) | 6 (1.6) | 1 (0.3) | 31 (23.7) | 3 (2.3) | 0 | 29 (22.0) | 3 (2.3) | 0 |
| Abdominal pain | 67 (17.6) | 6 (1.6) | 0 | 20 (15.3) | 2 (1.5) | 0 | 22 (16.7) | 6 (4.5) | 1 (0.8) |
| Other | |||||||||
| Fatigue | 137 (36.1) | 19 (5.0) | 0 | 55 (42.0) | 9 (6.9) | 0 | 41 (31.1) | 4 (3.0) | 0 |
| Decreased appetite | 88 (23.2) | 5 (1.3) | 1 (0.3) | 35 (26.7) | 2 (1.5) | 0 | 29 (22.0) | 3 (2.3) | 1 (0.8) |
| Pyrexia | 78 (20.5) | 2 (0.5) | 0 | 16 (12.2) | 0 | 0 | 23 (17.4) | 2(1.5) | 0 |
| Headache | 65 (17.1) | 4 (1.1) | 0 | 19 (14.5) | 3 (2.3) | 0 | 19 (14.4) | 3 (2.3) | 0 |
| Cough | 55 (14.5) | 1 (0.3) | 0 | 21 (16.0) | 0 | 0 | 18 (13.6) | 0 | 0 |
| Dyspnea | 46 (12.1) | 12 (3.2) | 2 (0.5) | 19 (14.5) | 4 (3.1) | 1 (0.8) | 25 (18.9) | 6 (4.5) | 0 |
| Anemia | 41 (10.8) | 11 (2.9) | 0 | 15 (11.5) | 4 (3.1) | 0 | 23 (17.4) | 11 (8.3) | 0 |
| Any immune-related event | 221 (58.2) | 37 (9.7) | 2 (0.5) | 80 (61.1) | 16 (12.2) | 3 (2.3) | 42 (31.8) | 4 (3.0) | 0 |
| Dermatologic | 152 (40.0) | 8 (2.1) | 1 (0.3) | 57 (43.5) | 2 (1.5) | 0 | 22 (16.7) | 0 | 0 |
| Pruritus | 67 (17.6) | 1 (0.3) | 0 | 32 (24.4) | 0 | 0 | 14 (10.6) | 0 | 0 |
| Rash | 67 (17.6) | 5 (1.3) | 0 | 25 (19.1) | 1 (0.8) | 0 | 6 (4.5) | 0 | 0 |
| Vitiligo | 14 (3.7) | 0 | 0 | 3 (2.3) | 0 | 0 | 1 (0.8) | 0 | 0 |
| Gastrointestinal | 122 (32.1) | 20 (5.3) | 2 (0.5) | 38 (29.0) | 10 (7.6) | 0 | 19 (14.4) | 1 (0.8) | 0 |
| Diarrhea | 115 (30.3) | 14 (3.7) | 0 | 36 (27.5) | 6 (4.6) | 0 | 18 (13.6) | 1 (0.8) | 0 |
| Colitis | 20 (5.3) | 11 (2.9) | 1 (0.3) | 10 (7.6) | 7 (5.3) | 0 | 1 (0.8) | 0 | 0 |
| Endocrine | 15 (3.9) | 4 (1.1) | 0 | 10 (7.6) | 3 (2.3) | 2 (1.5) | 2 (1.5) | 0 | 0 |
| Hypothyroidism | 6 (1.6) | 1 (0.3) | 0 | 2 (1.5) | 0 | 0 | 2 (1.5) | 0 | 0 |
| Hypopituitarism | 3 (0.8) | 2 (0.5) | 0 | 3 (2.3) | 1 (0.8) | 1 (0.8) | 0 | 0 | 0 |
| Hypophysitis | 2 (0.5) | 2 (0.5) | 0 | 2 (1.5) | 2 (1.5) | 0 | 0 | 0 | 0 |
| Adrenal insufficiency | 3 (0.8) | 2 (0.5) | 0 | 2 (1.5) | 0 | 0 | 0 | 0 | 0 |
| Increase in serum thyrotropin level | 2 (0.5) | 0 | 0 | 1 (0.8) | 0 | 0 | 0 | 0 | 0 |
| Decrease in serum corticotropin level | 0 | 0 | 0 | 2 (1.5) | 0 | 1 (0.8) | 0 | 0 | 0 |
| Hepatic | 8 (2.1) | 4 (1.1) | 0 | 5 (3.8) | 0 | 0 | 6 (4.5) | 3 (2.3) | 0 |
| Increase in alanine aminotransferase | 3 (0.8) | 2 (0.5) | 0 | 2 (1.5) | 0 | 0 | 3 (2.3) | 0 | 0 |
| Increase in aspartate aminotransferase | 4(1.1) | 1 (0.3) | 0 | 1 (0.8) | 0 | 0 | 2 (1.5) | 0 | 0 |
| Hepatitis | 2 (0.5) | 1 (0.3) | 0 | 1 (0.8) | 0 | 0 | 0 | 0 | 0 |
| Other | 12 (3.2) | 5 (1.3) | 0 | 6 (4.6) | 2 (1.5) | 1 (0.8) | 3 (2.3) | 1 (0.8) | 0 |
The adverse events listed here were reported in at least 15% of patients. The most common immune-related adverse events and those of particular clinical relevance are also listed. Patients could have more than one adverse event. Included are all patients who received at least one dose of a study drug (643 patients). A total of 14 deaths (2.2%) were determined by the investigators to be related to the study drug (8 in the ipilimumab-plus-gp100 group, 4 in the ipilimumab-alone group, and 2 in the gp100-alone group). Seven of the 14 deaths related to the study drug were associated with immune-related adverse events: 5 in the ipilimumab-plus-gp100 group (1 patient had grade 3 colitis and septicemia; 3 patients had bowel perforation–inflammatory colitis, bowel perforation, or multiorgan failure–peritonitis; and 1 patient had Guillain–Barré syndrome, which is considered to be consistent with a neurologic immune-related adverse event) and 2 in the ipilimumab-alone group (1 patient had colic bowel perforation and the other had liver failure). Deaths related to the study drug that were not associated with immune-related adverse events included deaths from sepsis, myelofibrosis, and acute respiratory distress syndrome (3 patients in the ipilimumab-plus-gp100 group); severe infection–renal failure–septic shock, and vascular leak syndrome (2 patients in the ipilimumab-alone group), and cachexia and septic shock (2 patients in the gp100-alone group).