Open-Label, Phase 2 Study of Blinatumomab As Second Salvage Therapy in Adults with Relapsed/Refractory Aggressive B-Cell Non-Hodgkin Lymphoma

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.400-400
• Main Authors: Coyle, Luke, Morley, Nicholas J., Rambaldi, Alessandro, Mason, Kylie D., Verhoef, Gregor, Furness, Caroline, Zhang, Alicia, Jung, A. Scott, Franklin, Janet L.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-112280

Background: Autologous hematopoietic stem cell transplantation (autoHSCT) following response to salvage chemotherapy is the standard of care for patients with relapsed/refractory (r/r) aggressive B-cell lymphoma after first-line chemotherapy. Patients without complete metabolic response (CMR) to first salvage (S1) therapy have limited options and poor outcomes based on historical data. Blinatumomab, a bispecific T-cell engager (BiTE®) antibody construct that directs cytotoxic T cells to lyse B cells expressing CD19, has demonstrated a survival benefit in B-cell acute lymphoblastic leukemia and has antitumor activity in patients with r/r aggressive B-cell non-Hodgkin lymphoma (B-NHL), including patients previously treated with autoHSCT. This open-label, multicenter, phase 2 portion of an adaptive phase 2/3 study (ClinicalTrials.gov, NCT02910063) assessed the efficacy and safety of blinatumomab as a second salvage (S2) therapy for patients with aggressive r/r NHL who have not achieved CMR following platinum-based S1 chemotherapy. Methods: Patients ≥18 years had biopsy-confirmed r/r aggressive B-NHL without a prior complete remission or CMR after first-line treatment with an anthracycline and anti-CD20 agent, and had either progressive metabolic disease (PMD), no metabolic response (NMR), or partial metabolic response (PMR; Lugano Classification) after ≥2 cycles of platinum-based S1 therapy. Patients with prior radiotherapy were PET+ ≥6 weeks after the last dose. Blinatumomab was given by continuous intravenous infusion for a single 70-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 14-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). The primary endpoint was CMR by central PET. Additional endpoints were objective response rate (ORR [CMR + PMR]), post-response HSCT realization rates, and the incidence/severity of adverse events (AEs). Results: Of the 41 patients enrolled, most had PMD/progressive disease (66%) and had refractory (68%) or relapsed (32%) disease; 5 (12%) had NMR, and 9 (22%) had PMR (Table). All 41 patients received blinatumomab; 19 (46%) completed cycle 1 (Table). Twenty-two patients discontinued cycle 1 (disease progression, n=17; AE n=4; death, n=1). Among the 17 patients who discontinued cycle 1 due to disease progression, 8 (47%) completed at least 90% of planned treatment duration. Four patients started cycl