MITI URL correction:
MITI had disclosed the following AE's (where 1 pt had died from MT103) at ASH 2008:
abstracts.hematologylibrary.org
Blood (ASH Annual Meeting Abstracts) 2008 112: Abstract 267
© 2008 American Society of Hematology Nov 2008
Articles by Bargou, R. C
Articles by Zugmaier, G.
Articles by Bargou, R. C
Articles by Zugmaier, G.
Oral Session
Targeted Therapies and New Agents in Lymphoma
Sustained Response Duration Seen after Treatment with Single Agent Blinatumomab (MT103/MEDI-538) in the Ongoing Phase I Study MT103- 104 in Patients with Relapsed NHL
Ralf C Bargou, MD1,*, Peter Kufer, MD2,*, Mariele Goebeler, MD3,*, Stefan Knop, MD4,*, Hermann Einsele, MD5, Richard Noppeney, MD6,*, Andreas Viardot, MD7,*, Patrick A Baeuerle, PhD2,*, Carsten Reinhardt, MD2,*, Margit Schmidt, PhD2,*, Petra Klappers2,*, Dirk Nagorsen, MD2,* and Gerhard Zugmaier, MD2,*
1 Internal Medicine II, University Hospital Würzburg, Würzburg, Germany, 2 Micromet AG, Munich, Germany, 3 Department of Internal Medicine II, Division of Hematology, University Hospital Würzburg, 4 Hematology & Oncology, Medical Center University of Wuerzburg, Wuerzburg, Germany, 5 Medizinische Klinik II, Wurzburg, Germany, 6 Center for Internal Medicine, Hematology, University Hospital Essen, Essen, Germany, 7 Internal Medicine III, Hematology, University Hospital Ulm, Ulm, Germany
Abstract
Introduction: Blinatumomab (MT103/MEDI-538), a BiTE antibody targeting the CD19 antigen, is a member of a novel class of molecules that redirect T cells for lysis of target cells. A Phase 1 dose escalation study is being conducted in patients with advanced NHL.
Methods: Relapsed NHL patients requiring treatment were included. Most patients were pre-treated, with a median of 3 previous chemo/immunotherapy regimens. To date, 7 dose levels ranging from 0.0005 to 0.09 mg/m2/24 h have been tested. Blinatumomab was continuously infused as single agent over a period of 4–8 weeks. Objective responses were assessed by Cheson criteria and centrally reviewed.
Results: To date 39 patients have been treated. Most common adverse events (AEs) included lymphopenia, pyrexia, and leukopenia. The majority of AEs (>95%) improved or resolved during treatment. Permanent treatment discontinuation due to AEs occurred in a total of 8 patients, of which 6 had fully reversible CNS events. One patient with a history of nearly fatal sepsis, pre-existing hypogammaglobulinemia and bone marrow affection by chemotherapy, experienced a fatal sepsis 5 weeks after treatment start. Dose-dependent activity was observed in mantle cell lymphoma, follicular lymphoma and CLL with responses observed in 11 out of 27 patients treated at doses of 0.015 mg/m2/24 h and higher. Five of those patients had complete and six had partial responses. At the dose level of 0.060 mg/m2/24 h, 7 out of 7 patients have shown objective responses. Beside one relapse after 14 months, no treatment failure has so far been observed for responders at dose levels of 0.030 mg/m2/24 h and 0.060 mg/m2/24 h. Five patients at these dose levels have ongoing responses for more than 6 months. Interestingly, partial remissions converted into complete remissions in two patients four weeks after end of infusion suggesting either reduction in lesion size due to efflux of a previously expanded T cell pool or prolonged T cell activity.
Conclusions: Blinatumomab as single agent induced apparently durable responses in pre-treated B-NHL patients with the highest response rate at a dose level of 0.06 mg/m2/24 h. Recruitment is ongoing.
Footnotes
Corresponding author
Disclosures: Bargou: Micromet: Consultancy. Kufer: Micromet: Employment. Baeuerle: Micromet: Employment. Reinhardt: Micromet: Employment. Schmidt: Micromet: Employment. Klappers: Micromet: Employment. Nagorsen: Micromet: Employment. Zugmaier: Micromet: Employment. |
