title: Safety, efficacy, and pharmacokinetics/pharmacodynamics of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma.
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.
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Berkowitz
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Janik
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Donn M
authors.initials: DM
authors.lastname: Stewart
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Maryalice
authors.initials: M
authors.lastname: Stetler-Stevenson
authors.affiliation: Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Joanna H
authors.initials: JH
authors.lastname: Shih
authors.affiliation: Clinical Pathology Department, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Fleisher
authors.affiliation: Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Turner
authors.affiliation: Department of Haematology and Pathology, University of the West Indies, Kingston, Jamaica.
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Urquhart
authors.affiliation: Department of Haematology and Pathology, University of the West Indies, Kingston, Jamaica.
authors.forename: Gilian H
authors.initials: GH
authors.lastname: Wharfe
authors.affiliation: Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
authors.affiliation: Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Cody J
authors.initials: CJ
authors.lastname: Peer
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Carolyn K
authors.initials: CK
authors.lastname: Goldman
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: tawald@helix.nih.gov.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Waldmann
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D000077561:Daclizumab; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; D000077561:Daclizumab
keywords: Adult T-cell leukemia/lymphoma; Daclizumab; Human T-cell leukemia virus 1 (HTLV-1) associated ATL; Interleukin-2 receptor alpha; Monoclonal antibody