Format

Send to

Choose Destination
J Clin Oncol. 2016 Apr 1;34(10):1104-11. doi: 10.1200/JCO.2014.59.1586. Epub 2016 Feb 16.

Bispecific T-Cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma: Final Results From a Phase I Study.

Author information

1
Maria-Elisabeth Goebeler, Stefan Knop, Max S. Topp, Hermann Einsele, and Ralf C. Bargou, Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg; Andreas Viardot, University Ulm; Peter Kufer, Gerhard Zugmaier, Matthias Klinger, Andreas Wolf, Margit Schmidt, and Patrick A. Baeuerle, Amgen Research (Munich); Brigitte Dorsch, Metronomia Clinical Research, Munich; Richard Noppeney, University of Essen Medical Center, Essen; Georg Hess, Johannes Gutenberg-University, Mainz; Stefan Kallert and Andreas Mackensen, University of Erlangen Medical Center, Erlangen; Kathrin Rupertus and Lothar Kanz, University of Tübingen Medical Center, Tübingen; Martin Libicher, Diakoniekrankenhaus Schwäbisch-Hall, Schwäbisch-Hall; Jürgen Scheele, University of Freiburg Medical Center; Eugen Leo, LEOConsulting, Freiburg, Germany; and Dirk Nagorsen and Beate D. Quednau, Amgen, Thousand Oaks, CA. goebeler_m@ukw.de.
2
Maria-Elisabeth Goebeler, Stefan Knop, Max S. Topp, Hermann Einsele, and Ralf C. Bargou, Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg; Andreas Viardot, University Ulm; Peter Kufer, Gerhard Zugmaier, Matthias Klinger, Andreas Wolf, Margit Schmidt, and Patrick A. Baeuerle, Amgen Research (Munich); Brigitte Dorsch, Metronomia Clinical Research, Munich; Richard Noppeney, University of Essen Medical Center, Essen; Georg Hess, Johannes Gutenberg-University, Mainz; Stefan Kallert and Andreas Mackensen, University of Erlangen Medical Center, Erlangen; Kathrin Rupertus and Lothar Kanz, University of Tübingen Medical Center, Tübingen; Martin Libicher, Diakoniekrankenhaus Schwäbisch-Hall, Schwäbisch-Hall; Jürgen Scheele, University of Freiburg Medical Center; Eugen Leo, LEOConsulting, Freiburg, Germany; and Dirk Nagorsen and Beate D. Quednau, Amgen, Thousand Oaks, CA.

Abstract

PURPOSE:

Blinatumomab is a CD19/CD3 BiTE (bispecific T-cell engager) antibody construct for the treatment of Philadelphia chromosome-negative acute B-lymphoblastic leukemia. We evaluated blinatumomab in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).

PATIENTS AND METHODS:

This 3 + 3 design, phase I dose-escalation study determined adverse events and the maximum tolerated dose (MTD) of continuous intravenous infusion blinatumomab in patients with relapsed/refractory NHL. Blinatumomab was administered over 4 or 8 weeks at seven different dose levels (0.5 to 90 μg/m(2)/day). End points were incidence of adverse events, pharmacokinetics, pharmacodynamics, and overall response rate.

RESULTS:

Between 2004 and 2011, 76 heavily pretreated patients with relapsed/refractory NHL, who included 14 with diffuse large B-cell lymphoma, were enrolled; 42 received treatment in the formal dose-escalation phase. Neurologic events were dose limiting, and 60 μg/m(2)/day was established as the MTD. Thirty-four additional patients were recruited to evaluate antilymphoma activity and strategies for mitigating neurologic events at a prespecified MTD. Stepwise dosing (5 to 60 μg/m(2)/day) plus pentosan polysulfate SP54 (n = 3) resulted in no treatment discontinuations; single-step (n = 5) and double-step (n = 24) dosing entailed two and seven treatment discontinuations due to neurologic events, respectively. Grade 3 neurologic events occurred in 22% of patients (no grade 4/5). Among patients treated at 60 μg/m(2)/day (target dose; n = 35), the overall response rate was 69% across NHL subtypes and 55% for diffuse large B-cell lymphoma (n = 11); median response duration was 404 days (95% CI, 207 to 1,129 days).

CONCLUSION:

In this phase I study of relapsed/refractory NHL, continuous infusion with CD19-targeted immunotherapy blinatumomab at various doses and schedules was feasible, with an MTD of 60 μg/m(2)/day. Single-agent blinatumomab showed antilymphoma activity.

PMID:
26884582
DOI:
10.1200/JCO.2014.59.1586
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center