Open-Label, Phase 2 Study of Blinatumomab after First-Line Rituximab-Chemotherapy in Adults with Newly Diagnosed, High-Risk Diffuse Large B-Cell Lymphoma

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.4077-4077
• Main Authors: Katz, Deborah A., Chu, Michael P., David, Kevin A., Thieblemont, Catherine, Morley, Nicholas J., Khan, Sharif S., Chen, Yuqi, Kalabus, James, Morris, Joan, Anderson, Abraham, Avilion, Ariel A., González-Barca, Eva
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-121708

Background: Rituximab combined with chemotherapy (R-chemotherapy) is the standard of care first-line treatment for diffuse large B-cell lymphoma (DLBCL). Despite success with R-chemotherapy, 30% to 50% of patients with high-risk DLBCL will relapse, and outcomes are poor among patients who relapse within one year of diagnosis. Given the challenge of successful salvage, novel first-line therapies are needed. Blinatumomab, a bispecific T-cell engager (BiTE®) antibody construct that directs cytotoxic T cells to lyse CD19-expressing B cells, has shown efficacy as salvage therapy in patients with relapsed or refractory DLBCL. This open-label, multicenter, phase 2 study (ClinicalTrials.gov, NCT03023878) assessed the efficacy and safety of blinatumomab after first-line R-chemotherapy for patients with newly diagnosed, high-risk DLBCL. Methods: Patients (≥18 y) had proven high-risk DLBCL (International Prognostic Index [IPI] 3−5 and double/triple hit or double MYC/BCL2 expressor) and Eastern Cooperative Oncology group performance status ≤2. To be eligible for blinatumomab, patients were required to achieve complete metabolic response (CMR), partial metabolic response (PMR), or stable metabolic response by PET/CT after a run-in period with 6 cycles of R-chemotherapy (R-CHOP, R-DA-EPOCH, or R-CHOEP). Blinatumomab was given by continuous intravenous infusion in a single 84-day cycle 1 (9 μg/day for 7 days, 28 μg/day for 7 days, and 112 μg/day for 42 days, followed by a 28-day treatment-free interval) and an optional 28-day cycle 2 (9 μg/day for 7 days, 28 μg/day for 7 days, and 112 μg/day for 14 days) for patients without progressive metabolic disease (PMD). The primary endpoint was the incidence and severity of adverse events (AEs). Additional endpoints were objective response rate (ORR [CMR + PMR]) per Lugano criteria, minimal residual disease (MRD) by plasma cell−free circulating tumor DNA, overall survival (OS), and pharmacokinetics (PK). Results: Of 47 patients enrolled, 17 (36%) discontinued R-chemotherapy run-in (protocol criteria, n=6; patient request, n=5; disease progression, n=3; ineligibility, n=1; AE, n=1; death, n=1) and 30 (64%) completed the run-in (2 did not proceed to blinatumomab). Of 28 patients who received blinatumomab, 26 (93%) had high or high-intermediate IPI; 8 (29%) were double/triple hit and 10 (36%) were double protein expressors (Table). In total, 26 (93%) patients completed cycle 1; ten of 11 (91%) patients completed optional cycle 2. Bl