Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma

• Verfasst von: Viardot, Andreas [VerfasserIn]
• Verfasst von: Nagorsen, Dirk [VerfasserIn]
• Titel: Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma
• Verf.angabe: Andreas Viardot, Marie-Elisabeth Goebeler, Georg Hess, Svenja Neumann, Michael Pfreundschuh, Nicole Adrian, Florian Zettl, Martin Libicher, Cyrus Sayehli, Julia Stieglmaier, Alicia Zhang, Dirk Nagorsen, and Ralf C. Bargou
• E-Jahr: 2016
• Jahr: January 11, 2016
• Umfang: 7 S.
• Fussnoten: Gesehen am 31.10.2019
• Titel Quelle: Enthalten in: Blood
• Ort Quelle: Washington, DC : American Society of Hematology, 1946
• Jahr Quelle: 2016
• Band/Heft Quelle: 127(2016), 11, Seite 1410-1416
• ISSN Quelle: 1528-0020
• DOI: doi:10.1182/blood-2015-06-651380
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1680805509

Abstract

Few patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) achieve prolonged disease-free survival. Blinatumomab, a bispecific T-cell engaging antibody construct, transiently links CD3-positive T cells to CD19-positive B cells. This phase 2 study evaluated stepwise (9-28-112 μg/d with weekly dose increases; n = 23) or flat (112 μg/d; n = 2) dosing of blinatumomab by continuous infusion, with dexamethasone prophylaxis, in patients with relapsed/refractory DLBCL. Patients received a median of 3 prior lines of therapy. Median time since last regimen was 1.5 months. Seventeen patients ended treatment in cycle 1 (induction), 7 in cycle 2 (consolidation), and 1 in retreatment. Among 21 evaluable patients, the overall response rate after 1 blinatumomab cycle was 43%, including complete responses (CRs) in 19%. Three patients had late CR in follow-up without other treatment. The most common adverse events with stepwise dosing were tremor (48%), pyrexia (44%), fatigue (26%), and edema (26%). Grade 3 neurologic events with stepwise dosing were encephalopathy and aphasia (each 9%) and tremor, speech disorder, dizziness, somnolence, and disorientation (each 4%). Of 5 (22%) patients who discontinued stepwise dosing because of adverse events, 4 (17%) had neurologic events. Most neurologic events resolved. The flat-dose cohort was stopped because of grade 3 neurologic events in both patients. Blinatumomab monotherapy appears effective in patients with relapsed/refractory DLBCL, a heavily pretreated patient population with a high unmet medical need. Further studies need to define the optimal approach to achieve the target dose without early dropout.