90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin's lymphoma

John E. Janik, John C. Morris, Deirdre O'Mahony, Stefania Pittaluga, Elaine S. Jaffe, Christophe E. Redon, William M. Bonner, Martin W. Brechbiel, Chang H. Paik, Millie Whatley, Clara Chen, Jae Ho Lee, Thomas A. Fleisher, Maggie Brown, Jeffrey D. White, Donn M. Stewart, Suzanne Fioravanti, Cathryn C. Lee, Carolyn K. Goldman, Bonita R. BryantRichard P. Junghans, Jorge A. Carrasquillo, Tat'Yana Worthy, Erin Corcoran, Kevin C. Conlon, Thomas A. Waldmann

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 90Y-daclizumab. 90Y provides strong β emissions that kill tumor cells at a distance by a crossfire effect. In 46 evaluable HL patients treated with 90Y-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 90Y-daclizumab infusions directed predominantly toward nonmalignant T cells rosetting around Reed-Sternberg cells provided meaningful therapy for select HL patients.

Original languageEnglish (US)
Pages (from-to)13045-13050
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number42
DOIs
StatePublished - Oct 20 2015

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Hodgkin Disease
Antibody Formation
Reed-Sternberg Cells
Monoclonal Antibodies
T-Lymphocytes
Bone Marrow
Radioimmunotherapy
Tumor Microenvironment
Interleukin-2 Receptors
Myelodysplastic Syndromes
Regulatory T-Lymphocytes
daclizumab
Karyotype
DNA Damage
Anti-Idiotypic Antibodies
Therapeutics
Clinical Trials
Recurrence
Neoplasms

Keywords

  • Hodgkin's lymphoma
  • Myelodysplastic syndrome
  • Radioimmunotherapy
  • Y-daclizumab

ASJC Scopus subject areas

  • General

Cite this

90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin's lymphoma. / Janik, John E.; Morris, John C.; O'Mahony, Deirdre; Pittaluga, Stefania; Jaffe, Elaine S.; Redon, Christophe E.; Bonner, William M.; Brechbiel, Martin W.; Paik, Chang H.; Whatley, Millie; Chen, Clara; Lee, Jae Ho; Fleisher, Thomas A.; Brown, Maggie; White, Jeffrey D.; Stewart, Donn M.; Fioravanti, Suzanne; Lee, Cathryn C.; Goldman, Carolyn K.; Bryant, Bonita R.; Junghans, Richard P.; Carrasquillo, Jorge A.; Worthy, Tat'Yana; Corcoran, Erin; Conlon, Kevin C.; Waldmann, Thomas A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 42, 20.10.2015, p. 13045-13050.

Research output: Contribution to journalArticle

Janik, JE, Morris, JC, O'Mahony, D, Pittaluga, S, Jaffe, ES, Redon, CE, Bonner, WM, Brechbiel, MW, Paik, CH, Whatley, M, Chen, C, Lee, JH, Fleisher, TA, Brown, M, White, JD, Stewart, DM, Fioravanti, S, Lee, CC, Goldman, CK, Bryant, BR, Junghans, RP, Carrasquillo, JA, Worthy, TY, Corcoran, E, Conlon, KC & Waldmann, TA 2015, '90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin's lymphoma', Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 42, pp. 13045-13050. https://doi.org/10.1073/pnas.1516107112
Janik, John E. ; Morris, John C. ; O'Mahony, Deirdre ; Pittaluga, Stefania ; Jaffe, Elaine S. ; Redon, Christophe E. ; Bonner, William M. ; Brechbiel, Martin W. ; Paik, Chang H. ; Whatley, Millie ; Chen, Clara ; Lee, Jae Ho ; Fleisher, Thomas A. ; Brown, Maggie ; White, Jeffrey D. ; Stewart, Donn M. ; Fioravanti, Suzanne ; Lee, Cathryn C. ; Goldman, Carolyn K. ; Bryant, Bonita R. ; Junghans, Richard P. ; Carrasquillo, Jorge A. ; Worthy, Tat'Yana ; Corcoran, Erin ; Conlon, Kevin C. ; Waldmann, Thomas A. / 90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin's lymphoma. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 42. pp. 13045-13050.
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AU - Janik, John E.

AU - Morris, John C.

AU - O'Mahony, Deirdre

AU - Pittaluga, Stefania

AU - Jaffe, Elaine S.

AU - Redon, Christophe E.

AU - Bonner, William M.

AU - Brechbiel, Martin W.

AU - Paik, Chang H.

AU - Whatley, Millie

AU - Chen, Clara

AU - Lee, Jae Ho

AU - Fleisher, Thomas A.

AU - Brown, Maggie

AU - White, Jeffrey D.

AU - Stewart, Donn M.

AU - Fioravanti, Suzanne

AU - Lee, Cathryn C.

AU - Goldman, Carolyn K.

AU - Bryant, Bonita R.

AU - Junghans, Richard P.

AU - Carrasquillo, Jorge A.

AU - Worthy, Tat'Yana

AU - Corcoran, Erin

AU - Conlon, Kevin C.

AU - Waldmann, Thomas A.

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