Confirmatory open-label, single-arm, multicenter phase 2 study of the BiTE antibody blinatumomab in patients (pts) with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL).

Leukemia, Myelodysplasia, and Transplantation
Session Type and Session Title: 
Oral Abstract Session, Leukemia, Myelodysplasia, and Transplantation
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 7005^)
Max S. Topp, Nicola Goekbuget, Anthony Selwyn Stein, Ralf C. Bargou, Hervé Dombret, Adele K. Fielding, Josep M. Ribera, Robin Foà, Gerhard Zugmaier, Chris Holland, Tapan Maniar, Birgit Huber, Dirk Nagorsen, Hagop M. Kantarjian; Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany; Department of Medicine II, Goethe University, Frankfurt, Germany; City of Hope, Duarte, CA; Comprehensive Cancer Center Mainfranken, Universitätsklinikum Würzburg, Würzburg, Germany; University Paris, Hôpital Saint-Louis, Paris, France; Department of Hematology, UCL, London, United Kingdom; ICO-Hospital Germans Trias i Pujol, Jose Carreras Research Institute, UAB, Badalona, Spain; Division of Hematology, Sapienza University, Rome, Italy; Amgen Research (Munich) GmbH, Munich, Germany; Amgen Rockville, Inc., Rockville, MD; Amgen Inc., Thousand Oaks, CA; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: Blinatumomab, an investigational bispecific T-cell engaging (BiTE) antibody that directs cytotoxic T-cells to CD19-expressing target cells, has shown antileukemia activity in an exploratory study in adult r/r B-precursor ALL. We evaluated blinatumomab efficacy and toxicity in a large confirmatory phase 2 study. Methods: Pts (≥18 yrs) with Ph-negative r/r ALL (refractory; 1st relapse <12 mo; relapse post HSCT <12 mo; ≥2ndsalvage) were eligible. Blinatumomab was given by continuous IV infusion (4 wks on/2 wks off) for up to 5 cycles (cycle 1 only: 9 μg/d days 1-7; then 28 μg/d). The primary endpoint was complete remission (CR) or CR with partial hematological recovery (CRh*) within the first 2 cycles. Results: 189 pts were enrolled and received blinatumomab for a median (range) of 2 (1–5) cycles. Median age was 39 (18–79) yrs. As of Jan 2014 (primary analysis in Feb 2014), 43% of pts achieved CR/CRh*; 80% of responses occurred within cycle 1. CRs/CRh* were seen in all subgroups (Table). Regardless of causality, the most frequent adverse events (AEs) were pyrexia (59%), headache (35%) and febrile neutropenia (29%). The most frequent gr ≥3 AEs were febrile neutropenia (26%), anemia (15%) and neutropenia (15%); 2% had gr ≥3 cytokine release syndrome. The most common gr ≥3 nervous system disorders were headache (4%), encephalopathy (3%) and ataxia (2%). 3 (2%) pts had gr 5 AEs considered treatment-related (sepsis, n=2; candida infection, n=1). Conclusions: This large phase 2 study confirmed the antileukemia activity of single-agent blinatumomab in a difficult-to-treat population with r/r ALL. Clinical trial information: NCT01466179.

Endpoint All patients
CR/CRh*, n (%)a
Prior aHSCT (n=64)
No prior aHSCT:
No prior salvage (n=25)
1 prior salvage (n=47)
≥2 prior salvages or primary refractory (n=53)
82 (43)
95% CI, 36%–51%
30 (47)

10 (40)
24 (51)
18 (34)
CR, n (%)a 64 (34)
CRh*, n (%)a 18 (10)
Median relapse-free survival, mo (95% CI) 5.9 (5.0–8.4)
Median OS, mo (95% CI) 6.1 (4.2–7.5)
Exploratory Responders
Minimal residual disease (MRD) response, n (%)a 61 (74)

Abbreviation: aHSCT, allogeneic stem cell transplantation. a First two cycles (central review).