title: Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma.
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. The study was registered at www.clinicaltrials.gov as #NCT01741792.
authors.affiliation: Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany;
authors.forename: Andreas
authors.initials: A
authors.lastname: Viardot
authors.affiliation: Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany;
authors.forename: Marie-Elisabeth
authors.initials: ME
authors.lastname: Goebeler
authors.affiliation: Department of Hematology, Oncology, and Pneumology, Johannes Gutenberg-University, Mainz, Germany;
authors.forename: Georg
authors.initials: G
authors.lastname: Hess
authors.affiliation: Medical Department II, University Hospital Schleswig Holstein Campus Kiel, Kiel, Germany;
authors.forename: Svenja
authors.initials: S
authors.lastname: Neumann
authors.affiliation: Klinik für Innere Medizin I, Saarland University Medical School, Homburg (Saar), Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.affiliation: Klinik für Innere Medizin I, Saarland University Medical School, Homburg (Saar), Germany;
authors.forename: Nicole
authors.initials: N
authors.lastname: Adrian
authors.affiliation: University Hospital Göttingen, Göttingen, Germany;
authors.forename: Florian
authors.initials: F
authors.lastname: Zettl
authors.affiliation: Department of Radiology, Diakoniekrankenhaus Schwäbisch-Hall, Schwäbisch-Hall, Germany;
authors.forename: Martin
authors.initials: M
authors.lastname: Libicher
authors.affiliation: Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany;
authors.forename: Cyrus
authors.initials: C
authors.lastname: Sayehli
authors.affiliation: Amgen Research (Munich), Munich, Germany;
authors.forename: Julia
authors.initials: J
authors.lastname: Stieglmaier
authors.affiliation: Amgen Inc, Thousand Oaks, CA; and.
authors.forename: Alicia
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Amgen Inc, Thousand Oaks, CA; and.
authors.forename: Dirk
authors.initials: D
authors.lastname: Nagorsen
authors.affiliation: Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Ralf C
authors.initials: RC
authors.lastname: Bargou
mesh_terms: D000328:Adult; D000368:Aged; D018033:Antibodies, Bispecific / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D018941:Antigens, CD19 / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D017252:CD3 Complex / Q000276:immunology; D003907:Dexamethasone / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007167:Immunotherapy; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009422:Nervous System Diseases / Q000139:chemically induced; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy; D047368:Tumor Burden
chemical_list: D018033:Antibodies, Bispecific; D018941:Antigens, CD19; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D017252:CD3 Complex; C510808:blinatumomab; D003907:Dexamethasone