, Volume 57, Issue 8, pp 2233-2240
Date: 21 Mar 2012

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

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Introduction

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 [36]. 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 adverse even ...