Interferon‐alpha antibodies in patients with renal cell carcinoma treated with recombinant interferon‐alpha‐2A in an adjuvant multicenter trial

Abstract

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‐α2a) (9 × 106 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‐α2a antibodies. Results. Of 86 IFN‐treated patients observed for more than 2 months, 40 (47%) had IFN‐α2a‐binding and 25 (29%) had IFN‐α2a‐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‐α), 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‐α2a should be monitored for the presence and clinical relevance of IFN‐α antibodies to determine those who could respond to alternative treatment. Copyright © 1993 American Cancer Society