INTERFERON-ALPHA ANTIBODIES IN PATIENTS WITH RENAL-CELL CARCINOMA TREATED WITH RECOMBINANT INTERFERON-ALPHA-2A IN AN ADJUVANT MULTICENTER TRIAL

Background. Prolonged therapy with interferon (IFN) may lead to the formation of IFN antibodies. Methods. Patients with renal cell carcinoma (n = 270) with advanced localized disease were randomized after complete tumor resection to receive treatment with adjuvant recombinant IFN-alpha-2a (rIFN-alpha2a) (9 x 10(6) IU subcutaneously, three times per week for a maximum of 12 months) versus no treatment. Patients (IFN-treated group, 106 patients; control group, 97 patients) were monitored for the presence of rIFN-alpha2a antibodies. Results. Of 86 IFN-treated patients observed for more than 2 months, 40 (47%) had IFN-alpha2a-binding and 25 (29%) had IFN-alpha2a-neutralizing antibodies developed within a median of 3 and 6 months, respectively. A distinct peak in binding antibody titers occurred at 6-9 months. Therapy-induced neutralizing antibodies were equally reactive with two other recombinant IFN-alpha-2 subtypes but poorly recognized natural IFN-alpha (IFN-alpha), recombinant IFN-alpha-1/alpha-8, and recombinant IFN-omega-1. The duration of remission and rate of relapse were independent of the antibody status, although neutralizing and most nonneutralizing antibodies correlated with a reduction in the IFN-induced increase in beta-2-microglobulin levels. Conclusions. Patients treated with IFN-alpha2a should be monitored for the presence and clinical relevance of IFN-alpha antibodies to determine those who could respond to alternative treatment.