Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia.
We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data.
Department of Medicine, University Hospital, Goethe University, Frankfurt, Germany.
N
N
Gökbuget
Center for Observational Research, Thousand Oaks, CA, Amgen, USA.
M
M
Kelsh
Center for Observational Research, Thousand Oaks, CA, Amgen, USA.
V
V
Chia
Department of Hematology/Oncology, Cleveland Clinic, Cleveland, OH, USA.
A
A
Advani
Unità Operativa Complessa di Ematologia, Ospedale dell'Angelo, Mestre-Venezia, Italy.
R
R
Bassan
Blood Disease Department (Leukemia Unit), Hôpital Saint-Louis, Paris, France.
H
H
Dombret
Department of Internal Medicine - Hematology and Oncology, University Hospital, Brno, Czech Republic.
M
M
Doubek
Research Department of Haematology, UCL Cancer Institute, London, UK.
A K
AK
Fielding
Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
S
S
Giebel
Department of Biostatistics, Uxbridge, Amgen Ltd, UK.
V
V
Haddad
Department of Medicine, University Hospital, Goethe University, Frankfurt, Germany.
D
D
Hoelzer
Department of Biostatistics, Amgen Inc., Rockville, MD, USA.
C
C
Holland
Blood Diseases Service, Center Hospitalier Universitaire, Angers, France.
N
N
Ifrah
Center for Observational Research, Thousand Oaks, CA, Amgen, USA.
A
A
Katz
Department of Clinical Development, Amgen Inc., Thousand Oaks, CA, USA.
T
T
Maniar
Institute of Hematology and Medical Oncology "L. and A. Seragnoli" S. Orsola University Hospital, Bologna, Italy.
G
G
Martinelli
Clinical Hematology Department, ICO-Hospital Germans Trias I Pujol. Jose Carreras Research Institute, Barcelona, Spain.
M
M
Morgades
Department of Leukemia, University of Texas MD Cancer Center, Houston, TX, USA.
S
S
O'Brien
Clinical Hematology Department, ICO-Hospital Germans Trias I Pujol. Jose Carreras Research Institute, Barcelona, Spain.
J-M
JM
Ribera
Department of Hematology and Bone Marrow Transplantation, Rambam Medical Center, Haifa, Israel.
J M
JM
Rowe
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
A
A
Stein
Medizinische Klinik und Poliklinik II, Universitätsklinikums Würzburg, Würzburg, Germany.
M
M
Topp
Department of Medicine, Dana Farber Cancer Institute, Boston, MA, USA.
M
M
Wadleigh
Department of Leukemia, University of Texas MD Cancer Center, Houston, TX, USA.
H
H
Kantarjian
Lancet Oncol. 2012 Apr;13(4):403-11
22357140
JAMA. 2007 Jan 17;297(3):314-6
17227985
N Engl J Med. 2014 Oct 16;371(16):1507-17
25317870
Leukemia. 2007 Sep;21(9):1907-14
17611565
Cancer Causes Control. 2015 Nov;26(11):1627-42
26376890
Haematologica. 2016 Dec;101(12 ):1524-1533
27587380
Stat Med. 2004 Oct 15;23(19):2937-60
15351954
Clin Cancer Res. 2015 Sep 15;21(18):4035-9
26374073
Leukemia. 1997 Dec;11(12):2039-44
9447817
Blood. 2012 Sep 6;120(10):2032-41
22493293
Blood. 2012 Jun 28;119(26):6226-33
22592608
Blood. 2007 Feb 1;109(3):944-50
17032921
Cancer. 2008 Dec 1;113(11):3186-91
18846563
J Clin Oncol. 2011 Feb 10;29(5):532-43
21220592
Epidemiology. 2000 Sep;11(5):550-60
10955408
Haematologica. 2010 Apr;95(4):589-96
20145276
Clin Pharmacol Ther. 2015 May;97(5):502-7
25676488
Lancet Oncol. 2015 Jan;16(1):57-66
25524800
Epidemiology. 2000 Sep;11(5):561-70
10955409
Cancer. 2010 Dec 15;116(24):5568-74
20737576