242 Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) Following Blinatumomab-Induced Remission in Pediatric Patients with Relapsed/Refractory (r/r) B-Precursor Acute Lymphoblastic Leukemia (ALL): Preliminary Results from a Phase I/II Stud

Track: Poster Abstracts
Wednesday, February 11, 2015, 6:45 PM-7:45 PM
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
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