Interferon-alpha antibodies in patients with renal cell carcinoma treated with recombinant interferon-alpha-2A in an adjuvant multicenter trial. The Delta-P Study Group.
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-alpha 2a) (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-alpha 2a antibodies.


RESULTS
Of 86 IFN-treated patients observed for more than 2 months, 40 (47%) had IFN-alpha 2a-binding and 25 (29%) had IFN-alpha 2a-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 non-neutralizing antibodies correlated with a reduction in the IFN-induced increase in beta-2-microglobulin levels.


CONCLUSIONS
Patients treated with IFN-alpha 2a should be monitored for the presence and clinical relevance of IFN-alpha antibodies to determine those who could respond to alternative treatment.
Prümmer
O
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Department of Internal Medicine III, University of Ulm, Germany.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000276:immunology* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins
D000906:Antibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins