FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 354:709-718 February 16, 2006 Number 7 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Koon, H. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

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.

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.

Full Text of this Article

This article has been cited by other articles:

• Kirkwood, J. M., Tarhini, A. A., Panelli, M. C., Moschos, S. J., Zarour, H. M., Butterfield, L. H., Gogas, H. J. (2008). Next Generation of Immunotherapy for Melanoma. JCO 26: 3445-3455 [Abstract] [Full Text]  
• Correale, P., Tagliaferri, P., Fioravanti, A., Del Vecchio, M. T., Remondo, C., Montagnani, F., Rotundo, M. S., Ginanneschi, C., Martellucci, I., Francini, E., Cusi, M. G., Tassone, P., Francini, G. (2008). Immunity Feedback and Clinical Outcome in Colon Cancer Patients Undergoing Chemoimmunotherapy with Gemcitabine + FOLFOX followed by Subcutaneous Granulocyte Macrophage Colony-Stimulating Factor and Aldesleukin (GOLFIG-1 Trial). Clin. Cancer Res. 14: 4192-4199 [Abstract] [Full Text]  
• Sittler, T., Zhou, J., Park, J., Yuen, N. K., Sarantopoulos, S., Mollick, J., Salgia, R., Giobbie-Hurder, A., Dranoff, G., Hodi, F. S. (2008). Concerted Potent Humoral Immune Responses to Autoantigens Are Associated with Tumor Destruction and Favorable Clinical Outcomes without Autoimmunity. Clin. Cancer Res. 14: 3896-3905 [Abstract] [Full Text]  
• Krumbholz, M., Faber, H., Steinmeyer, F., Hoffmann, L.-A., Kumpfel, T., Pellkofer, H., Derfuss, T., Ionescu, C., Starck, M., Hafner, C., Hohlfeld, R., Meinl, E. (2008). Interferon-{beta} increases BAFF levels in multiple sclerosis: implications for B cell autoimmunity. Brain 131: 1455-1463 [Abstract] [Full Text]  
• Dummer, R., Schadendorf, D. (2008). How Melanoma Is Treated in Real Life. Arch Dermatol 144: 664-665 [Full Text]  
• Adalid-Peralta, L., Godot, V., Colin, C., Krzysiek, R., Tran, T., Poignard, P., Venet, A., Hosmalin, A., Lebon, P., Rouzioux, C., Chene, G., Emilie, D., the Interprim ANRS 112 Study Group, (2008). Stimulation of the primary anti-HIV antibody response by IFN-{alpha} in patients with acute HIV-1 infection. J. Leukoc. Biol. 83: 1060-1067 [Abstract] [Full Text]  
• Rossi, C. R., Mocellin, S., Pasquali, S., Pilati, P., Nitti, D. (2008). N-Ratio: a Novel Independent Prognostic Factor for Patients with Stage-III Cutaneous Melanoma. Ann. Surg. Oncol. 15: 310-315 [Abstract] [Full Text]  
• Downey, S. G., Klapper, J. A., Smith, F. O., Yang, J. C., Sherry, R. M., Royal, R. E., Kammula, U. S., Hughes, M. S., Allen, T. E., Levy, C. L., Yellin, M., Nichol, G., White, D. E., Steinberg, S. M., Rosenberg, S. A. (2007). Prognostic Factors Related to Clinical Response in Patients with Metastatic Melanoma Treated by CTL-Associated Antigen-4 Blockade. Clin. Cancer Res. 13: 6681-6688 [Abstract] [Full Text]  
• Kaae, J., Wohlfahrt, J., Boyd, H. A., Wulf, H. C., Biggar, R. J., Melbye, M. (2007). The Impact of Autoimmune Diseases on the Incidence and Prognosis of Cutaneous Malignant Melanoma. Cancer Epidemiol. Biomarkers Prev. 16: 1840-1844 [Abstract] [Full Text]  
• McDermott, D. F., Atkins, M. B. (2007). More Support for the Judicious Use of High-Dose Interleukin-2 in Patients With Advanced Melanoma. JCO 25: 3791-3793 [Full Text]  
• Tarhini, A. A., Kirkwood, J. M., Gooding, W. E., Cai, C., Agarwala, S. S. (2007). Durable Complete Responses With High-Dose Bolus Interleukin-2 in Patients With Metastatic Melanoma Who Have Experienced Progression After Biochemotherapy. JCO 25: 3802-3807 [Abstract] [Full Text]  
• BRACCI, L., PROIETTI, E., BELARDELLI, F. (2007). IFN-{alpha} and Novel Strategies of Combination Therapy for Cancer. Ann. N. Y. Acad. Sci. 1112: 256-268 [Abstract] [Full Text]  
• Gollob, J. A., Sciambi, C. J. (2007). Decitabine Up-regulates S100A2 Expression and Synergizes with IFN-{gamma} to Kill Uveal Melanoma Cells. Clin. Cancer Res. 13: 5219-5225 [Abstract] [Full Text]  
• Jacob, J. B., Kong, Y.-c. M., Meroueh, C., Snower, D. P., David, C. S., Ho, Y.-S., Wei, W.-Z. (2007). Control of Her-2 Tumor Immunity and Thyroid Autoimmunity by MHC and Regulatory T Cells. Cancer Res. 67: 7020-7027 [Abstract] [Full Text]  
• MONTERO, E., ALONSO, L., PEREZ, R., LAGE, A. (2007). Interleukin-2 Mastering Regulation in Cancer and Autoimmunity. Ann. N. Y. Acad. Sci. 1107: 239-250 [Abstract] [Full Text]  
• Joseph, K. R., Difazio, M. P., Hartman, K. R., Ney, J. P. (2007). NEUROCUTANEOUS MELANOSIS ASSOCIATED WITH AUTOIMMUNE DIABETES MELLITUS. Neurology 68: 1862-1863 [Full Text]  
• Yurkovetsky, Z. R., Kirkwood, J. M., Edington, H. D., Marrangoni, A. M., Velikokhatnaya, L., Winans, M. T., Gorelik, E., Lokshin, A. E. (2007). Multiplex Analysis of Serum Cytokines in Melanoma Patients Treated with Interferon-{alpha}2b. Clin. Cancer Res. 13: 2422-2428 [Abstract] [Full Text]  
• Rotondi, M., Minelli, R., Magri, F., Leporati, P., Romagnani, P., Baroni, M. C., Delsignore, R., Serio, M., Chiovato, L. (2007). Serum CXCL10 levels and occurrence of thyroid dysfunction in patients treated with interferon-{alpha} therapy for hepatitis C virus-related hepatitis. Eur J Endocrinol 156: 409-414 [Abstract] [Full Text]  
• Voltz, R. (2007). Can antibodies in serum predict the presence of microscopic tumors?. Neurology 68: 887-888 [Full Text]  
• Nesslinger, N. J., Sahota, R. A., Stone, B., Johnson, K., Chima, N., King, C., Rasmussen, D., Bishop, D., Rennie, P. S., Gleave, M., Blood, P., Pai, H., Ludgate, C., Nelson, B. H. (2007). Standard Treatments Induce Antigen-Specific Immune Responses in Prostate Cancer. Clin. Cancer Res. 13: 1493-1502 [Abstract] [Full Text]  
• Wang, W., Edington, H. D., Rao, U. N.M., Jukic, D. M., Land, S. R., Ferrone, S., Kirkwood, J. M. (2007). Modulation of Signal Transducers and Activators of Transcription 1 and 3 Signaling in Melanoma by High-Dose IFN{alpha}2b. Clin. Cancer Res. 13: 1523-1531 [Abstract] [Full Text]  
• Robin, M., Andreu-Gallien, J., Schlageter, M.-H., Bengoufa, D., Guillemot, I., Pokorna, K., Robert, C., Larghero, J., Rousselot, P., Raffoux, E., Dombret, H., Fenaux, P., Pla, M., Charron, D., Padua, R.-A., Chomienne, C. (2006). Frequent antibody production against RAR{alpha} in both APL mice and patients. Blood 108: 1972-1974 [Abstract] [Full Text]  
• Chin, L., Garraway, L. A., Fisher, D. E. (2006). Malignant melanoma: genetics and therapeutics in the genomic era.. Genes Dev. 20: 2149-2182 [Abstract] [Full Text]  
• Kirkwood, J. M., Moschos, S., Wang, W. (2006). Strategies for the development of more effective adjuvant therapy of melanoma: current and future explorations of antibodies, cytokines, vaccines, and combinations.. Clin. Cancer Res. 12: 2331s-2336s [Abstract] [Full Text]  
• Atkins, M. B. (2006). Cytokine-based therapy and biochemotherapy for advanced melanoma.. Clin. Cancer Res. 12: 2353s-2358s [Abstract] [Full Text]  
• (2006). Linking Interferon Response with Autoimmunity. Journal Watch Dermatology 2006: 5-5 [Full Text]  
• Fister, K. (2006). What's new in the other general journals.. BMJ 332: 477-478 [Full Text]  
• Koon, H., Atkins, M. (2006). Autoimmunity and Immunotherapy for Cancer. NEJM 354: 758-760 [Full Text]