Digestive Diseases and Sciences

, Volume 57, Issue 8, pp 2233–2240 | Cite as

Pathologic Changes in Ipilimumab-Related Hepatitis in Patients with Metastatic Melanoma

  • David E. KleinerEmail author
  • David Berman
Case Report


Ipilimumab is a fully human, monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), an immune checkpoint molecule that negatively regulates T-cell activation [1]. It is hypothesized that CTLA-4 blockade can break peripheral tolerance to tumor antigens, promoting an antitumor immune response [2]. Ipilimumab has shown durable objective responses and encouraging long-term survival in phase II trials involving patients with metastatic melanoma [3, 4, 5, 6]. In a phase III, randomized controlled trial, ipilimumab monotherapy demonstrated a statistically significant improvement in overall survival in previously treated patients with metastatic melanoma [7]. Recently, the results of another phase III trial with ipilimumab were reported for previously untreated patients with metastatic melanoma, which showed a statistically significant improvement in overall survival for ipilimumab plus dacarbazine compared with dacarbazine alone [8]. The treatment-related...


Ipilimumab Drug-induced hepatitis CTLA-4 Immunosuppressive therapy Metastatic melanoma 



Adverse event


Alanine aminotransferase


Alkaline phosphatase


Aspartate aminotransferase


Cytotoxic T-lymphocyte antigen-4


Upper limit of normal



Editorial and writing assistance was provided by StemScientific, funded by Bristol-Myers Squibb Co. This research was supported in part by the Intramural Research Program of the US National Institutes of Health (National Cancer Institute).

Conflict of interest

David E. Kleiner: No financial, professional or personal conflicts of interest exist with respect to this work. David Berman is an employee of Bristol-Myers Squibb Company and discloses ownership of equity in the company.


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Copyright information

© Springer Science+Business Media, LLC (Outside the USA) 2012

Authors and Affiliations

  1. 1.Laboratory of PathologyNational Cancer InstituteBethesdaUSA
  2. 2.Research and Development–Global Clinical ResearchBristol-Myers Squibb CompanyPrincetonUSA

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