title: 90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin's lymphoma.
abstract: Despite significant advances in the treatment of Hodgkin's lymphoma (HL), a significant proportion of patients will not respond or will subsequently relapse. We identified CD25, the IL-2 receptor alpha subunit, as a favorable target for systemic radioimmunotherapy of HL. The scientific basis for the clinical trial was that, although most normal cells with exception of Treg cells do not express CD25, it is expressed by a minority of Reed-Sternberg cells and by most polyclonal T cells rosetting around Reed-Sternberg cells. Forty-six patients with refractory and relapsed HL were evaluated with up to seven i.v. infusions of the radiolabeled anti-CD25 antibody (90)Y-daclizumab. (90)Y provides strong β emissions that kill tumor cells at a distance by a crossfire effect. In 46 evaluable HL patients treated with (90)Y-daclizumab there were 14 complete responses and nine partial responses; 14 patients had stable disease, and nine progressed. Responses were observed both in patients whose Reed-Sternberg cells expressed CD25 and in those whose neoplastic cells were CD25(-) provided that associated rosetting T cells expressed CD25. As assessed using phosphorylated H2AX (γ-H2AX) as a bioindicator of the effects of radiation exposure, predominantly nonmalignant cells in the tumor microenvironment manifested DNA damage, as reflected by increased expression of γ-H2AX. Toxicities were transient bone-marrow suppression and myelodysplastic syndrome in six patients who had not been evaluated with bone-marrow karyotype analyses before therapy. In conclusion, repeated (90)Y-daclizumab infusions directed predominantly toward nonmalignant T cells rosetting around Reed-Sternberg cells provided meaningful therapy for select HL patients.
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
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;
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Deirdre
authors.initials: D
authors.lastname: O'Mahony
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.affiliation: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Christophe E
authors.initials: CE
authors.lastname: Redon
authors.affiliation: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: William M
authors.initials: WM
authors.lastname: Bonner
authors.affiliation: Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
authors.affiliation: Nuclear Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Chang H
authors.initials: CH
authors.lastname: Paik
authors.affiliation: Nuclear Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Millie
authors.initials: M
authors.lastname: Whatley
authors.affiliation: Nuclear Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Clara
authors.initials: C
authors.lastname: Chen
authors.affiliation: Nuclear Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Immunology Service, Clinical Pathology Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Fleisher
authors.affiliation: Immunology Service, Clinical Pathology Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Maggie
authors.initials: M
authors.lastname: Brown
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: White
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Donn M
authors.initials: DM
authors.lastname: Stewart
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Suzanne
authors.initials: S
authors.lastname: Fioravanti
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Cathryn C
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
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;
authors.forename: Bonita R
authors.initials: BR
authors.lastname: Bryant
authors.affiliation: Department of Medicine, Roger Williams Medical Center, Providence, RI 02908.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Junghans
authors.affiliation: Nuclear Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Carrasquillo
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Tat'Yana
authors.initials: T
authors.lastname: Worthy
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Erin
authors.initials: E
authors.lastname: Corcoran
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Conlon
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; tawald@helix.nih.gov.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Waldmann
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D000077561:Daclizumab; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D012008:Recurrence; D055815:Young Adult; D015021:Yttrium Radioisotopes / Q000737:chemistry*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; D015021:Yttrium Radioisotopes; D000077561:Daclizumab
keywords: 90Y-daclizumab; Hodgkin's lymphoma; myelodysplastic syndrome; radioimmunotherapy