PMID- 25619164 OWN - NLM STAT- MEDLINE DCOM- 20160202 LR - 20220408 IS - 2045-7634 (Electronic) IS - 2045-7634 (Print) IS - 2045-7634 (Linking) VI - 4 IP - 5 DP - 2015 May TI - CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations. PG - 661-72 LID - 10.1002/cam4.371 [doi] AB - Melanoma remains a critical public health problem worldwide. Patients with stage IV disease have very poor prognosis and their 1-year survival rate is only 25%. Until recently, systemic treatments with a positive impact on overall survival (OS) had remained elusive. In recent years, the United States Food and Drug Administration (FDA) - approved several novel agents targeting the RAS/RAF/MEK/ERK pathway (vemurafenib, dabrafenib, and trametinib) - critical in cell division and proliferation of melanoma, and an immune checkpoint inhibitor (ipilimumab) directed against the cytotoxic T lymphocyte Antigen - (CTLA-4). Moreover, recent reports of clinical trials studying other immune checkpoint modulating agents will most likely result in their FDA approval within the next months. This review focuses on ipilimumab, its safety and efficacy, and future considerations. Ipilimumab has demonstrated a positive OS impact after a several-year follow-up. It is also recognized that due to its mechanism of action, the response patterns to ipilimumab can differ from those observed in patients following treatment with conventional cytotoxic agents and even the most recently approved BRAF inhibitors. Most patients (84.8%) experience drug-related adverse events (AEs) of any grade; most of these are mild to moderate and immune mediated. However, a minority of patients may also experience severe and life-threatening AEs. In clinical studies, AEs were managed according to guidelines that emphasized close clinical monitoring and early use of corticosteroids when appropriate. Preliminary results have taught us the potential greater toxicity when in combination with vemurafenib, and the greater antitumor efficacy when combined with nivolumab, a monoclonal antibody directed against programmed death receptor-1 (PD-1), another immune checkpoint inhibitor. Future challenges include the optimization of dosing and toxicities when used as a single agent, and studying the safety and efficacy of combinations with targeted small molecules and other monoclonal antibodies to treat patients with melanoma and other malignancies. CI - (c) 2015 The Author. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Camacho, Luis H AU - Camacho LH AD - St. Luke's Cancer Center, Houston, Texas. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20150125 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antineoplastic Agents) RN - 0 (CTLA-4 Antigen) RN - 0 (Ipilimumab) SB - IM MH - Antibodies, Monoclonal/*pharmacology/*therapeutic use MH - Antineoplastic Agents/*pharmacology/*therapeutic use MH - CTLA-4 Antigen/*antagonists & inhibitors/metabolism MH - Combined Modality Therapy MH - Disease Management MH - Drug-Related Side Effects and Adverse Reactions MH - Humans MH - Ipilimumab MH - Melanoma/*drug therapy/mortality/pathology MH - Treatment Outcome PMC - PMC4430259 OTO - NOTNLM OT - CTLA-4 OT - CTLA4 OT - Melanoma OT - immunotherapy OT - ipilimumab OT - survival EDAT- 2015/01/27 06:00 MHDA- 2016/02/03 06:00 PMCR- 2015/05/01 CRDT- 2015/01/27 06:00 PHST- 2014/03/26 00:00 [received] PHST- 2014/09/26 00:00 [revised] PHST- 2014/09/29 00:00 [accepted] PHST- 2015/01/27 06:00 [entrez] PHST- 2015/01/27 06:00 [pubmed] PHST- 2016/02/03 06:00 [medline] PHST- 2015/05/01 00:00 [pmc-release] AID - 10.1002/cam4.371 [doi] PST - ppublish SO - Cancer Med. 2015 May;4(5):661-72. doi: 10.1002/cam4.371. Epub 2015 Jan 25.