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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 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
Pages (from-to)176-187
Number of pages12
JournalClinical Immunology
Volume155
Issue number2
DOIs
StatePublished - 1 Dec 2014
Externally publishedYes

Keywords

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

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