Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: impact of HLA class I antigen expression on outcome.

Sosman JA, Unger JM, Liu PY, Flaherty LE, Park MS, Kempf RA, Thompson JA, Terasaki PI, Sondak VK, Southwest Oncology Group
J Clin Oncol. 2002 20 (8): 2067-75

PMID: 11956267 · DOI:10.1200/JCO.2002.08.072

PURPOSE - An association between expression of > or = two of five HLA class I antigens (HLA-A2, HLA-A28, HLA-B44, HLA-B45, and HLA-C3; collectively called M5) and response to an allogeneic melanoma vaccine (Melacine; Corixa Corporation, Seattle, WA) has been described in stage IV melanoma. This study investigated whether class I antigen expression impacted relapse-free survival (RFS) after adjuvant therapy with this vaccine.

PATIENTS AND METHODS - We performed class I (HLA-A, HLA-B, and HLA-C) serotyping on patients enrolled onto Southwest Oncology Group Trial 9035, a randomized, observation-controlled, phase III trial of adjuvant Melacine. All patients had clinically node-negative cutaneous melanoma (1.5 to 4.0 mm). Interactions between treatment and class I antigen expression were tested. Analyses involved all serotyped patients and were adjusted for tumor thickness, method of nodal staging, sex, ulceration, and primary tumor site.

RESULTS - HLA typing was performed on 553 (80%) of the 689 enrolled patients (294 vaccinated and 259 observed). Expression of > or = two M5 antigens was associated with a superior vaccine treatment effect. Among patients who matched > or = two of the M5, the 97 vaccine-treated patients had improved RFS compared with the 78 observation patients (5-year relapse-free survival, 83% v 59%; P =.0002). The major components of this effect were contributed by HLA-A2 and HLA-C3. Among those who were HLA-A2-positive and/or HLA-C3-positive, the 5-year RFS for vaccinated patients was 77%, compared with 64% for observation (P =.004). There was no impact of HLA-A2 and/or HLA-C3 expression among observation patients.

CONCLUSION - This prospective analysis indicates a highly significant benefit of adjuvant therapy with Melacine among patients expressing > or = two of the M5 class I antigens, validating a prior observation in stage IV disease. HLA-A2 and HLA-C3 contributed most to this effect. Processed melanoma peptides found in Melacine may be presented by HLA-A2 and HLA-C3 and play a role in preventing relapse in vaccinated patients.

MeSH Terms (14)

Adjuvants, Immunologic Adult Aged Aged, 80 and over Cancer Vaccines Disease-Free Survival Female Histocompatibility Antigens Class I Humans Male Melanoma Middle Aged Prospective Studies Skin Neoplasms

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