Immunotherapy in the management of melanoma: current status

Figures & data

Figure 1 The B-RAF and N-RAS pathways for the development of malignant melanoma.

©2008. Elsevier. Reproduced with permission from Sekulic A, Haluska Jr P, Miller AJ et al. Malignant melanoma in the 21st century: the emerging molecular landscape. Mayo Clin Proc. 2008:83(7):825–846.

Table 1 Summary of the therapeutic target, relevant clinical trials, and common side effects of select melanoma immunotherapies

Immunotherapy	Target	Current trials	Completed trials	Side effects
Ipilimumab*	Noncompliment-fixing IgG2 selectively binds to and inhibits CTLA-4, releasing an inhibitory influence and allowing full activation of the T-cell response	Currently, 67 trials are under way investigating combination therapy, efficacy, and safety. Search http://www.clinicaltrials.gov for more information	Phase II NCT00289640,** NCT00289627,** NCT00729950,** NCT00135408**	Exanthem, diarrhea, pruritis, colitis, inflammatory hepatotoxicity, hypophysitis, episcleritis^Citation66
Tremelimumab	Noncompliment-fixing IgG2 that selectively binds to and inhibits CTLA-4, releasing an inhibitory influence and allowing full activation of the T-cell response	Phase I NCT01103635**	Phase III trial – abandoned secondary to low response rates	Exanthem, diarrhea, pruritis, colitis, inflammatory hepatotoxicity, hypophysitis, episcleritis^Citation66
Vemurafenib*	Selective BRAF kinase inhibitor for melanoma containing the BRAF^V600E mutation	Currently, 31 trials are under way investigating combination therapy, efficacy, and safety. Search http://www.clinicaltrials.gov for more information	Numerous trials have concluded, including a recent phase II trial NCT00949702**	Squamous cell carcinoma, verrucous keratoses, lobular panniculitis, photosensitivity, keratosis pilaris, rash, fatigue, alopecia, keratoacanthoma, pruritis, nausea, diarrhea, hyperkeratosis^Citation67,Citation68
Allovectin-7	Intratumoral injection of a plasmid/lipid composite encoding HLA-B7and ß2 microglobulin that expresses foreign antigens and causes a local inflammatory response	Phase III NCT00395070,** phase III NCT00003647**	Phase II NCT00044356**	Injection site pain, rigors, fatigue, injection site erythema, myalgia, pyrexia, arthralgia, headache^Citation48
OncoVEX^GM-CSF	Intratumoral injection of herpes simplex-1 virus encoding GM-CSF that selectively replicates within tumor cells, causing necrosis and lysis of the cell	Phase III NCT00769704,** phase III NCT01368276**	Phase II NCT00289016**	Fever, chills, fatigue/malaise, pain at injection site, headache, vomiting, diarrhea^Citation52,Citation69
PV-10	Intratumoral injection, leading to accumulation within the lysosome and subsequent autolysis of the tumor cell	Cleared for phase III trials to begin in late 2012	Phase II NCT00521053,** phase I NCT002198438**	Pain at treatment site, local inflammation, pruritis, photosensitivity^Citation55

Notes:

* Received Food and Drug Administration approval for treatment of unresectable or metastatic melanoma (2011);

** National Institutes of Health ClinicalTrials.gov reference number.

Abbreviations: CTLA-4, cytotoxic T lymphocyte antigen 4; GM-CSF, granulocyte macrophage colony-stimulating factor; Ig, immunoglobulin.

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