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

作者：Goebeler, Maria-Elisabeth^*; Knop, Stefan; Viardot, Andreas; Kufer, Peter; Topp, Max S.; Einsele, Hermann; Noppeney, Richard; Hess, Georg; Kallert, Stefan; Mackensen, Andreas; Rupertus, Kathrin; Kanz, Lothar; Libicher, Martin; Nagorsen, Dirk; Zugmaier, Gerhard; Klinger, Matthias; Wolf, Andreas; Dorsch, Brigitte; Quednau, Beate D.; Schmidt, Margit; Scheele, Juergen; Baeuerle, Patrick A.; Leo, Eugen; Bargou, Ralf C.

来源：Journal of Clinical Oncology, 2016, 34(10): 1104-+.

DOI：10.1200/JCO.2014.59.1586

• ACUTE LYMPHOBLASTIC-LEUKEMIA
• FOLLICULAR LYMPHOMA
• B-LINEAGE
• FREE SURVIVAL
• OPEN-LABEL
• AGENTS
• THERAPY
• TRANSPLANTATION
• DEXAMETHASONE
• CHEMOTHERAPY

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 mg/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 mg/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 mg/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 mg/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 mg/m(2)/day. Single-agent blinatumomab showed antilymphoma activity.

• 出版日期2016-4-1