Association of CTLA-4 Polymorphisms with Improved Overall Survival in Melanoma Patients Treated with CTLA-4 Blockade: A Pilot Study

• Published in: Cancer investigation 2013-06, Vol.31 (5), p.336-345
• Main Authors: Queirolo, P., Morabito, A., Laurent, S., Lastraioli, S., Piccioli, P., Ascierto, P. A., Gentilcore, G., Serra, M., Marasco, A., Tornari, E., Dozin, B., Pistillo, M. P.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Autoimmunity; Base Sequence; Biological and medical sciences; Case-Control Studies; Clinical Trials, Phase II as Topic; CTLA-4; CTLA-4 Antigen - antagonists & inhibitors; CTLA-4 Antigen - genetics; CTLA-4 blockade; Dermatology; Female; Gene Frequency; Genetic Association Studies; Humans; Ipilimumab; Kaplan-Meier Estimate; Male; Medical sciences; Melanoma; Melanoma - drug therapy; Melanoma - genetics; Melanoma - mortality; Melanoma - secondary; Middle Aged; Multicenter Studies as Topic; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Overall survival; Pharmacology. Drug treatments; Pilot Projects; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Single nucleotide polymorphisms; Skin Neoplasms - drug therapy; Skin Neoplasms - genetics; Skin Neoplasms - mortality; Skin Neoplasms - pathology; Treatment Outcome; Tumors; Tumors of the skin and soft tissue. Premalignant lesions
• ISSN: 0735-7907; 1532-4192
• DOI: 10.3109/07357907.2013.793699

CTLA-4 blockade with monoclonal antibodies can lead to cancer regression in patients with metastatic melanoma (MM). CTLA-4 gene polymorphisms may influence the response to anti-CTLA-4 antibodies although few data are available regarding this issue. We analyzed six CTLA-4 single nucleotide polymorphisms (−1661A>G, −1577G>A, −658C>T, −319C>T, +49A>G, and CT60G>A) in 14 Italian MM patients and 45 healthy subjects. We found a significant association between the −1577G/A and CT60G/A genotypes and improved overall survival (Pc < 0.006, Bonferroni corrected), further confirmed by the diplotype analysis (−1577&CT60 GG-AA diplotype, p < 0.001). A positive trend toward an association between these genotypes and response to therapy was also observed.