To the Editor: The finding by Robert et al.(June 30 issue) 1 that adding ipilimumab to dacarbazine chemotherapy in first-line therapy for metastatic melanoma improves survival is a landmark for immunotherapy. The authors leave readers with the impression that dacarbazine reduces the rate of ipilimumab-associated immune-related adverse events but causes manageable hepatotoxic effects. However, they do not make any recommendation about the future use of dacarbazine with ipilimumab. A comparison of the rate of grade 3 or 4 nonhepatic, immune-related adverse events in the present trial with that in the phase 3 trial of second-line ipilimumab at approximately one third the dose2 shows no significant difference (23 of 247 patients with events vs. 66 of 511 patients with events, P= 0.18 by the chi-square test). The corresponding rates of grade 3 or 4 diarrhea or colitis were 15 of 247 patients with events versus 39 of 511 patients with events (P= 0.53 by the chi-square test). Hence, ipilimumab plus dacarbazine does not seem to confer any benefit in reducing the frequency of grade 3 or 4 nonhepatic, immune-related adverse events, and it adds toxicity. The rate of grade 5 toxic events of zero in the present trial, as compared with 2.4% in the second-line trial, is encouraging and suggests that management of ipilimumabrelated adverse events has improved.