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Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma.
- Source :
-
Blood [Blood] 2016 Mar 17; Vol. 127 (11), pp. 1410-6. Date of Electronic Publication: 2016 Jan 11. - Publication Year :
- 2016
-
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.<br /> (© 2016 by The American Society of Hematology.)
- Subjects :
- Adult
Aged
Antibodies, Bispecific administration & dosage
Antibodies, Bispecific adverse effects
Antibodies, Bispecific immunology
Antigens, CD19 immunology
Antigens, Neoplasm immunology
Antineoplastic Agents administration & dosage
Antineoplastic Agents adverse effects
Antineoplastic Agents immunology
CD3 Complex immunology
Dexamethasone therapeutic use
Disease-Free Survival
Dose-Response Relationship, Drug
Drug Administration Schedule
Fatigue chemically induced
Female
Fever chemically induced
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Nervous System Diseases chemically induced
Recurrence
Remission Induction
Salvage Therapy
Tumor Burden
Antibodies, Bispecific therapeutic use
Antineoplastic Agents therapeutic use
Immunotherapy
Lymphoma, Large B-Cell, Diffuse drug therapy
Molecular Targeted Therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 127
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 26755709
- Full Text :
- https://doi.org/10.1182/blood-2015-06-651380