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

Program: Oral and Poster Abstracts
Type: Oral
Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: New Agents
Hematology Disease Topics & Pathways:
Adult, antibodies, Biological, Leukemia, Diseases, Therapies, DLBCL, Study Population, Clinically relevant, Lymphoid Malignancies
Sunday, December 2, 2018: 12:45 PM
Pacific Ballroom 20 (Marriott Marquis San Diego Marina)

Luke Coyle1*, Nicholas J. Morley2*, Alessandro Rambaldi, MD3, Kylie D. Mason, MBBS, MD, FRACP, FRCPA, PhD4, Gregor Verhoef, MD PhD5*, Caroline Furness6*, Alicia Zhang7*, A. Scott Jung8* and Janet L. Franklin8

1Departmenet of Haematology, Royal North Shore Hospital, Sydney, AUS
2Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
3Department of Oncology-Hematology, University of Milan and Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
4Department of Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia
5Department of Hematology, University Hospitals Leuven, Leuven, Belgium
6Haemato-Oncology, Royal Marsden NHS Foundation Trust, London, United Kingdom
7Global Biostatistical Science, Amgen Inc., Thousand Oaks, CA
8Global Development, Amgen Inc., Thousand Oaks, CA

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 cycle 2; 3 (7%) completed cycle 2. One patient discontinued cycle 2 due to AEs. The ORR (within 12 weeks of starting blinatumomab) was 37% (15/41 patients; 95% CI, 22%, 53%); 9 (22%) patients achieved CMR (Table). Eight (20%) patients had HSCT in remission, 7 (17%) with autoHSCT (CMR, n=6; PMR, n=1), and 1 with allogeneic HSCT in PMR. Thirty-five patients did not have HSCT (n=32) or had delayed HSCT (n=3) due to PMD (n=17), lack of CMR (n=4), AE (n=4), patient preference (n=1), NMR or unknown (n=1), and other (n=8); 1 patient had missing information. Eight of 9 CMR patients (89%) were alive without relapse, with a median follow up time of 8.8 months. The Kaplan-Meier estimate at 9 months was 51%; median overall survival (OS) was not reached (Table).

In total, 24 (59%) patients had grade ≥3 treatment-emergent AEs, and 10 (24%) had grade ≥4 treatment-emergent AEs. Seven (17%) patients discontinued treatment due to AEs. Consistent with previous blinatumomab reports, neurologic events (NEs) were reported in 23 (56%) patients, including 10 (24%) with grade 3 NEs and 3 (7%) with NEs leading to treatment discontinuation. Grade 3 cytokine release syndrome was reported in only 1 patient. Other grade ≥3 AEs included infections (n=8; 20%), bone marrow toxicity (n=7; 17%), thromboembolic events (n=3; 7%), hepatic disorders (n=2; 5%), and acute pancreatitis (n=1; 2%).

Conclusions: In patients with r/r aggressive B-NHL and predominantly progressive disease following ≥2 cycles of platinum-based S1 chemotherapy, blinatumomab monotherapy as S2 therapy induced CMR/PMR in 37% of patients and led to HSCT in 20%. When considering that 66% of the patients enrolled had progressive disease and that 47% received the therapeutic dose, blinatumomab showed promising efficacy consistent with the efficacy and safety demonstrated in earlier blinatumomab B-NHL trials and potentially offers a treatment option for patients unresponsive to standard salvage regimens.

Disclosures: Coyle: Amgen Inc.: Other: non-financial relationship. Morley: Amgen Inc.: Honoraria, Other: non-financial; Roche: Honoraria, Other: non-financial, Research Funding. Rambaldi: Celgene: Consultancy; Roche: Consultancy; Omeros: Consultancy; Italfarmaco: Consultancy; Novartis: Consultancy; Amgen Inc.: Consultancy; Pfizer: Consultancy. Zhang: Amgen Inc.: Employment, Equity Ownership. Jung: Amgen Inc.: Employment, Equity Ownership. Franklin: Amgen Inc.: Employment, Equity Ownership.

*signifies non-member of ASH