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

• Published in: Blood Vol. 127; no. 11; pp. 1410 - 1416
• Main Authors: Viardot, Andreas, Goebeler, Marie-Elisabeth, Hess, Georg, Neumann, Svenja, Pfreundschuh, Michael, Adrian, Nicole, Zettl, Florian, Libicher, Martin, Sayehli, Cyrus, Stieglmaier, Julia, Zhang, Alicia, Nagorsen, Dirk, Bargou, Ralf C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.03.2016; American Society of Hematology
• Subjects: Adult; Aged; Antibodies, Bispecific - administration & dosage; Antibodies, Bispecific - adverse effects; Antibodies, Bispecific - immunology; Antibodies, Bispecific - therapeutic use; Antigens, CD19 - immunology; Antigens, Neoplasm - immunology; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - immunology; Antineoplastic Agents - therapeutic use; CD3 Complex - immunology; Clinical Trials and Observations; Dexamethasone - therapeutic use; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Fatigue - chemically induced; Female; Fever - chemically induced; Humans; Immunotherapy; Kaplan-Meier Estimate; Lymphoma, Large B-Cell, Diffuse - drug therapy; Male; Middle Aged; Molecular Targeted Therapy; Nervous System Diseases - chemically induced; Recurrence; Remission Induction; Salvage Therapy; Tumor Burden
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2015-06-651380

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. •Among evaluable patients with relapsed/refractory DLBCL who received blinatumomab 112 μg/d, overall response was 43% (CR was 19%).•Blinatumomab continuous infusion was feasible with weekly stepwise dose escalation (9-28-112 μg/d) and dexamethasone prophylaxis.