Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease

D. Przepiorka, N. A. Kernan, C. Ippoliti, E. B. Papadopoulos, S. Giralt, I. Khouri, J. G. Lu, J. Gajewski, A. Durett, K. Cleary, R. Champlin, B. S. Andersson, S. Light

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    230 Scopus citations

    Abstract

    Daclizumab, a humanized monoclonal IgG1 directed against the α chain of the interleukin-2 receptor (IL-2R), is a competitive inhibitor of IL-2 on activated lymphocytes. To test the hypothesis that specific inhibition of activated lymphocytes in patients with ongoing acute graft-versus-host disease (GVHD) might ameliorate the process, we treated 43 patients with advanced or steroid-refractory GVHD with daclizumab. The first cohort of 24 patients was treated with daclizumab 1 mg/kg on days 1,8, 15, 22, and 29. On day 43, the complete response (CR) rate was 29% (95% confidence interval [Cl], 13%-51%). Survival on day 120 was 29% (95% Cl, 13%-51%). A second cohort of 19 patients was treated with daclizumab 1 mg/kg on days 1, 4, 8, 15, and 22. For these patients, the CR rate on day 43 was 47% (95% Cl, 24%- 71%), and survival on day 120 was 53% (95% Cl, 29%-76%). There were no infusion-related reactions and no serious side effects related to daclizumab. Following treatment, there was a reduction in serum concentrations of soluble IL-2R and peripheral blood CD3+25+ lymphocytes, but these changes were not predictive of response. Daclizumab has substantial activity for the treatment of acute GVHD, and the second regimen evaluated is recommended for a controlled study.

    Original languageEnglish (US)
    Pages (from-to)83-89
    Number of pages7
    JournalBlood
    Volume95
    Issue number1
    DOIs
    StatePublished - Jan 1 2000

    ASJC Scopus subject areas

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

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  • Cite this

    Przepiorka, D., Kernan, N. A., Ippoliti, C., Papadopoulos, E. B., Giralt, S., Khouri, I., Lu, J. G., Gajewski, J., Durett, A., Cleary, K., Champlin, R., Andersson, B. S., & Light, S. (2000). Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. Blood, 95(1), 83-89. https://doi.org/10.1182/blood.v95.1.83.001k18_83_89