Background Immunotherapy for advanced melanoma induces serologicand clinical manifestations of autoimmunity. We assessed theprognostic significance of autoimmunity in patients with stageIIB, IIC, or III melanoma who were treated with high-dose adjuvantinterferon alfa-2b.
Methods We enrolled 200 patients in a substudy of a larger,ongoing randomized trial. Blood was obtained before the initiationof intravenous interferon therapy, after 1 month of therapy,and at 3, 6, 9, and 12 months. Serum was tested for antithyroid,antinuclear, anti-DNA, and anticardiolipin autoantibodies, andpatients were examined for vitiligo.
Results The median duration of follow-up was 45.6 months. Relapseoccurred in 115 patients, and 82 patients died. The median relapse-freesurvival was 28.0 months, and the median overall survival was58.7 months. Autoantibodies and clinical manifestations of autoimmunitywere detected in 52 patients (26 percent). The median relapse-freesurvival was 16.0 months among patients without autoimmunity(108 of 148 had a relapse) and was not reached among patientswith autoimmunity (7 of 52 had a relapse). The median survivalwas 37.6 months among patients without autoimmunity (80 of 148died) and was not reached among patients with autoimmunity (2of 52 died). In univariate and multivariate regression analyses,autoimmunity was an independent prognostic marker for improvedrelapse-free survival and overall survival (P<0.001).
Conclusions The appearance of autoantibodies or clinical manifestationsof autoimmunity during treatment with interferon alfa-2b isassociated with statistically significant improvements in relapse-freesurvival and overall survival in patients with melanoma.
Source Information
From the First Department of Medicine, Laiko Hospital (H.G., A.P., C.M., D.B., D.P., G.F.) and the Department of Dermatology, Andreas Sygros Hospital (O.P., A.S.), National and Kapodistrian University of Athens; the Department of Plastic Surgery and Microsurgery (J.I., D.T., P.P.) and the Department of Immunology and National Tissue Typing Center (C.S.-G.), General Hospital of Athens; the Laboratory of Biostatistics, University of Athens School of Nursing (U.D.); and the Department of Pathology, Sotiria General Hospital, World Health Organization Melanoma Program (K.F.) — all in Athens, Greece; and the University of Pittsburgh Cancer Institute, Pittsburgh (J.M.K.).
Address reprint requests to Dr. Gogas at the University of Athens, First Department of Medicine, P.O. Box 14120, 115 10 Athens, Greece, or at hgogas{at}hol.gr.
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