Evaluation of CTLA-4 polymorphisms in high-risk melanoma patients receiving adjuvant interferon

Abstract

9054 Background: Attempts to identify patients who benefit from adjuvant treatment with interferon alfa-2b (IFN) have been disappointing. The development of autoimmunity during adjuvant therapy with IFN cannot assist selection of patients for therapy at baseline. Multiple polymorphisms within the CTLA-4 gene have been found to be associated with autoimmune diseases. We therefore evaluated six CTLA- 4 single nucleotide polymorphisms (SNPs) in high-risk melanoma patients enrolled in a study of two regimens of high-dose IFN and compared the distribution of SNPs found in healthy controls. Methods: We genotyped DNA from peripheral blood of 203 stage IIb, IIc and III melanoma patients and 288 healthy controls for 49 A/G, 60 C/T, 318 C/T, JO27, JO30 and JO31 using PCR and pyrosequencing technology (Biotage, Uppsala, Sweden). Results: At a median follow up of 57.3 months (95% CI 50.14–64.76), 115 patients have recurred and 58 have died. The median DFS was 42 months and the median OS has not been reached yet (mean OS: 65 months). There were no statistical significant differences in the incidence of CTLA-4 polymorphisms between melanoma patients and healthy controls. The tabular distribution of these polymorphisms in melanoma patients is presented below. RFS and OS did not differ significantly between patients with the alleles represented by these polymorphisms (p=0.90 and p=0.28 for 49 A/G, p=0.89 and p=0.9 for 60 C/T, p=0.63 and p=0.72 for 318 C/T, p=0.88 and p=0.69 for JO27, p=0.74 and p=0.97 for JO30, p=0.6 and p=0.92 for JO31 respectively). High association between the different polymorphisms was found (Fishers´ exact p-values <.001 for all associations). Conclusions: No polymorphism of CTLA4 defined by the SNPs studied was correlated with improved RFS or OS in this high-risk group of melanoma patients. 49A/G (%) 60 C/T (%) 318 CT (%) JO27 (%) JO30 (%) JO31 (%) A/A 46.3 A/G 53.2 C/C 79.8 T/C 53.7 G/A 51.7 G/T 52.7 A/G 43.3 A/A 22.2 C/T 19.2 C/C 23.6 A/A 24.1 T/T 23.2 G/G 10.3 G/G 24.6 T/T 1 T/T 22.7 G/G 24.1 G/G 24.1 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Schering-Plough