Correlation of molecular human leukocyte antigen typing and outcome in high‐risk melanoma patients receiving adjuvant interferon

Abstract

BACKGROUND: Interferon is approved for adjuvant treatment of patients with stage IIB/III melanoma. The identification of predictive markers that would permit selection of patients would be beneficial. Specific human leukocyte antigen (HLA) class I and II antigens have previously shown an association with response to therapy or overall survival of patients with metastatic melanoma. METHODS: A total of 284 high-risk melanoma patients participating in a randomized trial and 246 healthy controls were molecularly typed for HLA class I and II. Specific allele frequencies were compared between the healthy and patient populations, as well as presence or absence of these in relation to recurrence. Alleles related to autoimmune disease were also investigated. RESULTS: No significant differences were found between the distribution of HLA genotype in the melanoma population compared with healthy controls. Correlations between nonrecurrence and the presence of HLA-Cw*06 allele were noted present in 19.3% of melanoma patients. The median relapse-free survival of the Cw*06-positive cohort was 100.2 months versus 37.3 months in the Cw*06-negative cohort ( P = .013). The median overall survival for the Cw*06-positive cohort has not yet been reached, versus 78.9 months in the Cw*06-negative cohort ( P = .025). HLA-Cw*06 was present in 29.79% of patients in the autoimmunity group and 15.38% of patients in the nonautoimmunity group ( P = .049). CONCLUSIONS: No allele was associated with absence of recurrence in patients receiving adjuvant interferon with the exception of HLA-Cw*06, an allele correlated with psoriasis. HLA-Cw*06-positive patients have better relapse-free and overall survival. Cancer 2010. © 2010 American Cancer Society.

Adjuvant Treatment of Melanoma

“…The determination of HLA is also a factor predicting recurrence in patients treated with interferon 2b as adjuvant treatment. The percentage of relapses is significantly lower in patients with HLA genotype A33, HLA B57, HLA-Cw03, and HLA-Cw06 [65].…”

Adjuvant Vaccine Immunotherapy of Resected, Clinically Node-Negative Melanoma: Long-term Outcome and Impact of HLA Class I Antigen Expression on Overall Survival

“…Irrespective of the precise mechanism, the existence of a distinct and identifiable subset of patients with clinical benefit from allogeneic vaccination suggests continued exploration of immune-based adjuvant strategies in melanoma, with particular reference to melanoma-associated antigens present in Melacine and presented by HLA-A2 and HLA-Cw3. Moreover, the possibility of interactions between HLA haplotype and treatment with other types of immunotherapy, such as IFNα, ipilimumab, IL-2, anti-PD-1 or anti-PD-L1 antibody therapies, may deserve further study, although previous efforts to find such interactions have been inconclusive (14,15). …”

The use of interferon in melanoma patients: A systematic review

“…In another study assessing HLA alleles, a total of 284 high-risk melanoma patients participating in a randomized trial of HD-IFN compared with observation were typed for HLA class I and II. Patients positive for the Cw 06 allele had a significant advantage in median RFS (100.2 versus 37.3 months) and median OS (not reached versus 78.9 months) [83].…”

“…Patients homozygous for rs10964859 (HR = 2.01, 95% CI 1.17, 3.44; p = 0.01) and rs10964862 (HR 1.84, 95%CI 1.03, 3.27, p = 0.04) were associated to increased risk of death following metastasis Gogas et al [83] HLA gene The median relapse-free survival of the Cw 06-positive cohort was 100.2 months versus 37.3 months in the Cw 06-negative cohort (p = 0.013) Hofmann et al [86] Serum cytokines At baseline, the combination of TNF-a, B2 M and sIL-2R revealed a positive predictive value for relapse of 82.9% in the multivariate analyses lost, thereby demonstrating the lack of usefulness of serum autoantibodies as a prognostic factor [84].…”