Melanoma is the deadliest form of skin cancer. Ipilimumab, a novel 
immunotherapy, is the first treatment shown to improve survival in patients with 
metastatic melanoma in large randomized controlled studies. The most concerning 
side effects reported in clinical studies of ipilimumab fall into the category 
of immune-related adverse events, which include enterocolitis, dermatitis, 
thyroiditis, hepatitis, hypophysitis, uveitis, and others. During the course of 
routine clinical care at Mount Sinai Medical Center, frequent hepatotoxicity was 
noted when ipilimumab was administered at a dose of 3 mg/kg according to Food 
and Drug Administration (FDA) guidelines. To better characterize these adverse 
events, we conducted a retrospective review of the first 11 patients with 
metastatic melanoma treated with ipilimumab at the Mount Sinai Medical Center 
after FDA approval. Aspartate aminotransferase (AST) and alanine 
aminotransferase (ALT) elevation, as defined by the National Cancer Institute's 
Common Terminology Criteria for Adverse Events, each occurred in six of 11 cases 
(≥grade 1), a notably higher frequency than could be expected on the basis of 
the FDA licensing study where elevations were reported in 0.8 and 1.5% of 
patients for AST and ALT, respectively. Grade 3 elevations in AST occurred in 
three of 11 patients as compared with 0% in the licensing trial. All cases of 
transaminitis resolved when ipilimumab was temporarily withheld without 
administration of immunosuppressive medication. During routine clinical care of 
late-stage melanoma patients with ipilimumab, physicians should monitor patients 
closely for hepatotoxicity and be aware that toxicity rates may differ across 
populations during ipilimumab therapy.