EBV-related lymphoproliferative disease complicating therapy with the anti-CD2 monoclonal antibody, siplizumab, in patients with t-cell malignancies

Deirdre O'Mahony, John C. Morris, Maryalice Stetler-Stevenson, Helen Matthews, Margaret R. Brown, Thomas Fleisher, Stefania Pittaluga, Mark Raffeld, Paul S. Albert, Dirk Reitsma, Karen Kaucic, Luz Hammershaimb, Thomas A. Waldmann, John Edward Janik

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44 Scopus citations

Abstract

Purpose: We report an increased incidence of EBV-induced B-cell lymphoproliferative disease (LPD) in patients treated with siplizumab, an anti-CD2 antibody. The development of EBV-LPD has been associated with the use of immunosuppressive agents used in solid organ, bone marrow, and stem cell transplantation and in certain congenital immunodeficiencies. Experimental Design: We conducted a single-institution phase I dose-escalation trial of siplizumab, a humanized monoclonal antibody to CD2, in 29 patients withT-cell malignancies. Results: Although initial responses were encouraging, 4 (13.7%) patients developed EBV-LPD and the trial was stopped. Reductions in CD4+ and CD8+ cell count numbers in response to therapy were seen in all patients, but in those patients developing EBV-LPD a significantly greater reduction in natural killer (NK) cell number and CD2 expression onTcells was seen. These findings highlight the importance of NK-cell depletion and CD2 expression in addition to T-cell depletion in the etiology of EBV-LPD. Conclusions: The emergence of EBV-LPD may be associated with the ability of siplizumab to deplete both T and NK cells without affecting B cells. Agents that depleteT- and NK-cell populations without affecting B cell number should be screened for this potentially serious adverse event.

Original languageEnglish (US)
Pages (from-to)2514-2522
Number of pages9
JournalClinical Cancer Research
Volume15
Issue number7
DOIs
StatePublished - Apr 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    O'Mahony, D., Morris, J. C., Stetler-Stevenson, M., Matthews, H., Brown, M. R., Fleisher, T., Pittaluga, S., Raffeld, M., Albert, P. S., Reitsma, D., Kaucic, K., Hammershaimb, L., Waldmann, T. A., & Janik, J. E. (2009). EBV-related lymphoproliferative disease complicating therapy with the anti-CD2 monoclonal antibody, siplizumab, in patients with t-cell malignancies. Clinical Cancer Research, 15(7), 2514-2522. https://doi.org/10.1158/1078-0432.CCR-08-1254