Effective Natural Interferon-α Therapy in Recombinant Interferon-α-Resistant Patients With Hairy Cell Leukemia

• Published in: Blood 1991-07, Vol.78 (1), p.38-43
• Main Authors: Wussow, P. von, Pralle, H., Hochkeppel, H.-K., Jakschies, D., Sonnen, S., Schmidt, H., Miiller-Rosenau, D., Franke, M., Haferlach, T., Zwingers, T., Rapp, U., Deicher, H.
• Format: Article
• Language: English
• Subjects: Adult; Aged; DNA, Recombinant - genetics; Drug Evaluation; Drug Resistance - genetics; Female; Humans; Interferon Type I - genetics; Interferon Type I - standards; Interferon Type I - therapeutic use; Leukemia, Hairy Cell - drug therapy; Leukemia, Hairy Cell - genetics; Male; Middle Aged
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V78.1.38.38

To explore the relationship between anti-interferon-α (anti-IFN-α) antibodies and loss of clinical responsiveness to IFN-α treatment, we examined sera from 59 patients with hairy cell leukemia who responded to therapy with recombinant IFN-α-2a (rlFN-α-2a). During the first 2 years of therapy, 10 patients developed rlFN-α-2a-neutralizing and 15 HFN-α-2a-binding antibodies. Nine of the 59 initially responding patients became resistant to rlFN-α-2a and suffered a relapse of the disease at 7 to 24 months of treatment. All nine relapsing patients tested positive for both neutralizing and binding antibodies with titers above 400 INU/mL, while none of the antibody-negative patients relapsed. Six patients with detectable binding antibody titers below 400 INU/mL continued to respond to treatment. By measuring the IFN kinetics and the levels of the IFN-induced Mx-homologous protein in mononuclear cells after a single injection each of rlFN-α-2a and nlFN-α the IFN antibodies of eight of the nine resistant rIFN-α patients were found to be highly specific for rlFN-α-2a. Therefore, these eight patients were switched to natural IFN-α (nIFN-α) therapy at doses of 3 million IU, three times a week. All eight patients responded to treatment with nIFN-α, achieving durable objective responses similar to those obtained previously with rlFN-α-2a. These data clearly demonstrate that rlFN-α antibody-positive patients can effectively be treated with nIFN-α.