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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).
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
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.
|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)
95% CI, 36%–51%
|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)|
|Minimal residual disease (MRD) response, n (%)a||61 (74)|
Abbreviation: aHSCT, allogeneic stem cell transplantation. a First two cycles (central review).
Abstracts by Max S. Topp:
Updated phase I data of AFM13: A bispecific tandem antibody (TandAb) in relapsed/refractory (R/R) Hodgkin lymphoma (HL).Meeting: 2014 ASCO Annual Meeting | Abstract No: 3025^
Immunopharmacodynamic response to blinatumomab in patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL).Meeting: 2013 ASCO Annual Meeting | Abstract No: 7020
Presentations by Max S. Topp:
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).Meeting: 2014 ASCO Annual Meeting Abstract No: 7005^Session: Leukemia, Myelodysplasia, and Transplantation (Oral Abstract Session)