Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell–engaging CD19/CD3-bispecific BiTE antibody blinatumomab

DOI PDF 1 Citations
  • Matthias Klinger
    Amgen Research (Munich) GmbH, Munich, Germany;
  • Christian Brandl
    Amgen Research (Munich) GmbH, Munich, Germany;
  • Gerhard Zugmaier
    Amgen Research (Munich) GmbH, Munich, Germany;
  • Youssef Hijazi
    Amgen Research (Munich) GmbH, Munich, Germany;
  • Ralf C. Bargou
    Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany;
  • Max S. Topp
    Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany;
  • Nicola Gökbuget
    Medizinische Klinik II, Johann Wolfgang Goethe Universitätsklinikum, Frankfurt am Main, Germany;
  • Svenja Neumann
    II Medizinische Klinik und Poliklinik, Universitätsklinikum Schleswig-Holstein, Kiel, Germany;
  • Mariele Goebeler
    Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany;
  • Andreas Viardot
    Klinik für Innere Medizin III, Universitätsklinikum Ulm, Ulm, Germany; and
  • Matthias Stelljes
    Medizinische Klinik A, Universitätsklinikum Münster, Münster, Germany
  • Monika Brüggemann
    II Medizinische Klinik und Poliklinik, Universitätsklinikum Schleswig-Holstein, Kiel, Germany;
  • Dieter Hoelzer
    Medizinische Klinik II, Johann Wolfgang Goethe Universitätsklinikum, Frankfurt am Main, Germany;
  • Evelyn Degenhard
    Amgen Research (Munich) GmbH, Munich, Germany;
  • Dirk Nagorsen
    Amgen Research (Munich) GmbH, Munich, Germany;
  • Patrick A. Baeuerle
    Amgen Research (Munich) GmbH, Munich, Germany;
  • Andreas Wolf
    Amgen Research (Munich) GmbH, Munich, Germany;
  • Peter Kufer
    Amgen Research (Munich) GmbH, Munich, Germany;

Description

<jats:p>T cell–engaging CD19/CD3-bispecific BiTE Ab blinatumomab has shown an 80% complete molecular response rate and prolonged leukemia-free survival in patients with minimal residual B-lineage acute lymphoblastic leukemia (MRD+ B-ALL). Here, we report that lymphocytes in all patients of a phase 2 study responded to continuous infusion of blinatumomab in a strikingly similar fashion. After start of infusion, B-cell counts dropped to < 1 B cell/μL within an average of 2 days and remained essentially undetectable for the entire treatment period. By contrast, T-cell counts in all patients declined to a nadir within < 1 day and recovered to baseline within a few days. T cells then expanded and on average more than doubled over baseline within 2-3 weeks under continued infusion of blinatumomab. A significant percentage of reappearing CD8+ and CD4+ T cells newly expressed activation marker CD69. Shortly after start of infusion, a transient release of cytokines dominated by IL-10, IL-6, and IFN-γ was observed, which no longer occurred on start of a second treatment cycle. The response of lymphocytes in leukemic patients to continuous infusion of blinatumomab helps to better understand the mode of action of this and other globally T cell–engaging Abs. The trial is registered with www.clinicaltrials.gov identifier NCT00560794.</jats:p>

Journal

  • Blood

    Blood 119 (26), 6226-6233, 2012-06-28

    American Society of Hematology

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