Poster Abstracts
Grand Hall CD (Manchester Grand Hyatt)
Rupert Handgretinger
,
University of Tübingen, Tübingen, Germany
Lia Gore
,
Children’s Hospital Colorado, Aurora, CO
Gerhard Zugmaier
,
Amgen Research (Munich) GmbH, Munich, Germany
Franco Locatelli
,
Ospedale Pediatrico Bambino Gesu, University of Pavia, Rome, Italy
Christian M. Zwaan
,
Erasmus Medical Center, Sophia Children’s Hospital, Rotterdam, Netherlands
Deepa Bhojwani
,
St Jude Children's Research Hospital, Memphis, TN
Peter Bader
,
Hospital for Children and Adolescents, Department for Stem Cell Transplantation and Immunology, University of Frankfurt, Frankfurt, Germany
Maureen M. O'Brien
,
Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Tanya M. Trippett
,
Memorial Sloan-Kettering Cancer Center, New York, NY
Benoît Brethon
,
Service Hématologie-Immunologie Pédiatrique, Hôpital Robert Debré, Paris, France
Carmelo Rizzari
,
San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
Paul Gerhardt Schlegel
,
University Children’s Hospital Würzburg, Würzburg, Germany
Gérard Michel
,
Service d’hématologie pédiatrique, Hôpital de la Timone, Marseille, France
Phillip Barnette
,
Hematology/Oncology, Primary Children's Medical Center, Salt Lake City, UT
Chiara Messina
,
Clinica di Oncoematologia Pediatrica, Università degli Studi di Padova, Padova, Italy
Kuolung Hu
,
Amgen Inc., Thousand Oaks, CA
Noemi Mergen
,
Amgen Research (Munich) GmbH, Munich, Germany
Anja Fischer
,
Amgen Research (Munich) GmbH, Munich, Germany
James Whitlock
,
Hospital for Sick Children, Toronto, ON, Canada
Arend von Stackelberg
,
Charité Campus Virchow, Berlin, Germany
Presentation recording not available for download or distribution as requested by the presenting author.
The prognosis for patients (pts) with r/r ALL is poor especially after transplantation. Blinatumomab, an investigational bispecific T-cell engager (BiTE
®) antibody construct that redirects T cells to CD19
+ B cells resulting in serial lysis, has shown antileukemia activity in pts with r/r ALL. We evaluated the transplantation rate after blinatumomab-induced remission, in pediatric patients with r/r ALL characterized by negative prognostic factors, such as refractory disease and prior alloHSCT.
In this single-arm study, eligible pts were 2−18 yrs old and had an M3 marrow with B-precursor ALL that was refractory, in ≥2nd marrow relapse, or any marrow relapse after HSCT; and no CNS leukemia. A stepwise dose (wk 1: 5 µg/m²/d; thereafter: 15 µg/m²/d) of blinatumomab was given by continuous IV infusion (4 wks on/2 wks off) for up to 5 cycles. Primary endpoint was complete remission (CR) rate within 2 cycles. Secondary endpoints were alloHSCT rate, relapse-free survival (RFS), overall survival (OS), and adverse events (AEs).
39 pts received blinatumomab. Median (range) age was 9 (2–16) yrs. 69% of pts had ≥50% bone marrow blasts. 41% had 1 prior salvage, 41% had ≥2 prior salvages and 18% were primary refractory or had refractory relapse. 87% of pts enrolled had relapsed within 6 months after the last remission. Among pts with prior alloHSCT (64%), 16% had 1 relapse and 50% had ≥2 relapses. Of 12 pts (31%; 95% CI, 17%–48%) who reached CR within the first 2 cycles, 6 (50%) proceeded to alloHSCT. 5 pts who did not respond to blinatumomab received alloHSCT after treatment was ended. Donors included haploidentical parents (n=9), a sibling (n=1) and an unrelated donor (n=1). AlloHSCT were performed at 8 different centers. Conditioning regimens included 5 myeloablative, 5 reduced intensity, and 1 unknown regimen. Median (95% CI) RFS was 5.6 (2.6–12.1) months among blinatumomab responders and 6.5 (2.2–7.7) months among responders receiving alloHSCT (measured from the time of alloHSCT). At 6-month follow-up, median (95% CI) OS was 4.3 (3.6–8.1) months among all pts and 7.7 (0.45–NE) months among pts receiving alloHSCT (measured from the time of alloHSCT). 100-day mortality rate post alloHSCT was 10%. The most common AEs among all pts included pyrexia (74%), anemia (33%), nausea (31%), headache (28%) and hypertension (26%). Anemia (26%), pyrexia (21%), increased alanine aminotransferase or aspartate aminotransferase (18% each) and febrile neutropenia (15%) were the most common grade ≥3 AEs. 3 (8%) pts (2 with grade 3 events) had cytokine-release syndrome.
In this phase I/II study, blinatumomab has shown promising antileukemia activity in pediatric patients with r/r B-precursor ALL, most of whom had prior alloHSCT and/or were refractory. Half of pts who achieved CR in response to blinatumomab proceeded to alloHSCT, suggesting that blinatumomab may provide a therapeutic option to bridge this patient population to alloHSCT.
Disclosures:
L. Gore,
Amgen Inc., Participant in clinical trial:
Advisory Board
and
Consultancy
G. Zugmaier,
Amgen Inc., Executive director of clinical development:
Salary
F. Locatelli,
Amgen Inc., member of advisory committee:
Advisory Board
and
Honoraria
M. M. O'Brien,
Amgen Inc., Independent contractor:
Research Funding
Seattle Genetics, Independent consultant:
Advisory Board
and
Research Funding
Celgene, Advisory committee member:
Advisory Board
Epizyme, Independent consultant:
Research Funding
Novartis, Independent consultant:
Research Funding
T. M. Trippett,
Roche, Advisor:
Consultancy
Genentech, Advisor:
Consultancy
G. Michel,
Amgen Inc., Independent contractor:
Research Funding
K. Hu,
Amgen Inc., Statistician:
Salary
N. Mergen,
Amgen Research (Munich) GmbH, Employee:
Salary
A. Fischer,
Amgen Research (Munich) GmbH, CRSM:
Salary
A. von Stackelberg,
Amgen Inc., PI:
Consultancy
and
Honoraria