Resistance to Recombinant Interferon Alfa-2a in Hairy-Cell Leukemia Associated with Neutralizing Anti-Interferon Antibodies

Abstract

To explain the hematologic deterioration occasionally observed during interferon therapy, we assayed serum specimens from 51 patients with hairy-cell leukemia receiving treatment with recombinant interferon alfa-2a for the presence of anti-interferon antibodies. After a median of seven months of therapy, anti-interferon antibodies were found in 31 patients. Fifteen of these patients had only non-neutralizing antibodies, but antibody from the other 16 neutralized the antiviral effects of recombinant interferon alfa-2a in vitro. In no case, however, did neutralizing antibody inhibit the antiviral effects of purified natural interferon alfa. Clinical resistance to interferon of various degrees was present in 6 of 16 patients with neutralizing antibodies; the remaining 10 patients and all 20 patients without antibody continue to respond after a minimum of two years of therapy. In all the patients with interferon resistance, antibody was present when it developed.