Prognostic significance of autoimmunity during treatment of melanoma with interferon.
BACKGROUND
Immunotherapy for advanced melanoma induces serologic and clinical manifestations of autoimmunity. We assessed the prognostic significance of autoimmunity in patients with stage IIB, IIC, or III melanoma who were treated with high-dose adjuvant interferon alfa-2b.


METHODS
We enrolled 200 patients in a substudy of a larger, ongoing randomized trial. Blood was obtained before the initiation of 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, and patients were examined for vitiligo.


RESULTS
The median duration of follow-up was 45.6 months. Relapse occurred in 115 patients, and 82 patients died. The median relapse-free survival was 28.0 months, and the median overall survival was 58.7 months. Autoantibodies and clinical manifestations of autoimmunity were detected in 52 patients (26 percent). The median relapse-free survival was 16.0 months among patients without autoimmunity (108 of 148 had a relapse) and was not reached among patients with autoimmunity (7 of 52 had a relapse). The median survival was 37.6 months among patients without autoimmunity (80 of 148 died) and was not reached among patients with autoimmunity (2 of 52 died). In univariate and multivariate regression analyses, autoimmunity was an independent prognostic marker for improved relapse-free survival and overall survival (P<0.001).


CONCLUSIONS
The appearance of autoantibodies or clinical manifestations of autoimmunity during treatment with interferon alfa-2b is associated with statistically significant improvements in relapse-free survival and overall survival in patients with melanoma.
First Department of Medicine, Laiko Hospital, Athens, Greece. hgogas@hol.gr
Helen
H
Gogas
John
J
Ioannovich
Urania
U
Dafni
Catherine
C
Stavropoulou-Giokas
Konstantina
K
Frangia
Dimosthenis
D
Tsoutsos
Petros
P
Panagiotou
Aristidis
A
Polyzos
Othonas
O
Papadopoulos
Alexandros
A
Stratigos
Christos
C
Markopoulos
Dimitrios
D
Bafaloukos
Dimitrios
D
Pectasides
George
G
Fountzilas
John M
JM
Kirkwood
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D017024:Chemotherapy, Adjuvant; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011994:Recombinant Proteins; D012008:Recurrence; D012878:Skin Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D016019:Survival Analysis
D000276:Adjuvants, Immunologic; D001323:Autoantibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins