Safety, efficacy, and pharmacokinetics/pharmacodynamics of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma

Jonathan L. Berkowitz, John E. Janik, Donn M. Stewart, Elaine S. Jaffe, Maryalice Stetler-Stevenson, Joanna H. Shih, Thomas A. Fleisher, Maria Turner, Nicole E. Urquhart, Gilian H. Wharfe, William D. Figg, Cody J. Peer, Carolyn K. Goldman, Thomas A. Waldmann, John C. Morris

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Interleukin-2 receptor α chain (CD25) is overexpressed in human T-cell leukemia virus 1 associated adult T-cell leukemia/lymphoma (ATL). Daclizumab a humanized monoclonal antibody blocks IL-2 binding by recognizing the interleukin-2 receptor α chain (CD25). We conducted a phase I/II trial of daclizumab in 34 patients with ATL. Saturation of surface CD25 on circulating ATL cells was achieved at all doses; however saturation on ATL cells in lymph nodes required 8. mg/kg. Up to 8. mg/kg of daclizumab administered every 3. weeks was well tolerated. No responses were observed in 18 patients with acute or lymphoma ATL; however, 6 partial responses were observed in 16 chronic and smoldering ATL patients. The pharmacokinetics/pharmacodynamics of daclizumab suggest that high-dose daclizumab would be more effective than low-dose daclizumab in treatment of lymphoid malignancies and autoimmune diseases (e.g., multiple sclerosis) since high-dose daclizumab is required to saturate IL-2R alpha in extravascular sites.

Original languageEnglish (US)
Pages (from-to)176-187
Number of pages12
JournalClinical Immunology
Volume155
Issue number2
DOIs
Publication statusPublished - Dec 1 2014

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Keywords

  • Adult T-cell leukemia/lymphoma
  • Daclizumab
  • Human T-cell leukemia virus 1 (HTLV-1) associated ATL
  • Interleukin-2 receptor alpha
  • Monoclonal antibody

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Berkowitz, J. L., Janik, J. E., Stewart, D. M., Jaffe, E. S., Stetler-Stevenson, M., Shih, J. H., ... Morris, J. C. (2014). Safety, efficacy, and pharmacokinetics/pharmacodynamics of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma. Clinical Immunology, 155(2), 176-187. https://doi.org/10.1016/j.clim.2014.09.012