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
PurposeBlinatumomab 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 MethodsThis 3 + 3 design, phase...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
April 1, 2016
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| In: |
Journal of clinical oncology
Year: 2016, Volume: 34, Issue: 10, Pages: 1104-1111 |
| ISSN: | 1527-7755 |
| DOI: | 10.1200/JCO.2014.59.1586 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1200/JCO.2014.59.1586 Verlag, Volltext: https://ascopubs.org/doi/10.1200/JCO.2014.59.1586 
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| Author Notes: | Maria-Elisabeth Goebeler, Stefan Knop, Andreas Viardot, Peter Kufer, Max S. Topp, Hermann Einsele, Richard Noppeney, Georg Hess, Stefan Kallert, Andreas Mackensen, Kathrin Rupertus, Lothar Kanz, Martin Libicher, Dirk Nagorsen, Gerhard Zugmaier, Matthias Klinger, Andreas Wolf, Brigitte Dorsch, Beate D. Quednau, Margit Schmidt, Jürgen Scheele, Patrick A. Baeuerle, Eugen Leo, and Ralf C. Bargou |
| Summary: | PurposeBlinatumomab 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 MethodsThis 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/m2/day). End points were incidence of adverse events, pharmacokinetics, pharmacodynamics, and overall response rate.ResultsBetween 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/m2/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/m2/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/m2/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).ConclusionIn 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/m2/day. Single-agent blinatumomab showed antilymphoma activity. |
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| Item Description: | Gesehen am 05.11.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1527-7755 |
| DOI: | 10.1200/JCO.2014.59.1586 |