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

Goebeler ME, Knop S, Viardot A, Kufer P, Topp MS, Einsele H, Noppeney R, Hess G, Kallert S, Mackensen A, Rupertus K, Kanz L, Libicher M, Nagorsen D, Zugmaier G, Klinger M, Wolf A, Dorsch B, Quednau BD, Schmidt M, Scheele J, Baeuerle PA, Leo E, Bargou RC (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Journal of Clinical Oncology American Society of Clinical Oncology

Book Volume: 34

Pages Range: 1104-11

Journal Issue: 10

DOI: 10.1200/JCO.2014.59.1586

Abstract

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).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 ?g/m(2)/day). End points were incidence of adverse events, pharmacokinetics, pharmacodynamics, and overall response rate.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 ?g/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 ?g/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 ?g/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).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 ?g/m(2)/day. Single-agent blinatumomab showed antilymphoma activity.

Authors with CRIS profile

Andreas Mackensen Lehrstuhl für Innere Medizin V

Involved external institutions

Johannes Gutenberg-Universität Mainz (JGU) DE Germany (DE) Metronomia Clinical Research GmbH DE Germany (DE) Amgen Inc. US United States (USA) (US) Amgen GmbH DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE) LEOconsulting DE Germany (DE) Julius-Maximilians-Universität Würzburg DE Germany (DE) Universität Ulm DE Germany (DE) Universität Duisburg-Essen (UDE) DE Germany (DE) Eberhard Karls Universität Tübingen DE Germany (DE) Diakonie-Klinikum Schwäbisch Hall DE Germany (DE)

How to cite

APA:

Goebeler, M.-E., Knop, S., Viardot, A., Kufer, P., Topp, M.S., Einsele, H.,... Bargou, R.C. (2016). 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. Journal of Clinical Oncology, 34(10), 1104-11. https://doi.org/10.1200/JCO.2014.59.1586

MLA:

Goebeler, Maria-Elisabeth, et al. "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." Journal of Clinical Oncology 34.10 (2016): 1104-11.

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