PMID- 28355115
OWN - NLM
STAT- MEDLINE
DCOM- 20170913
LR  - 20220330
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 35
IP  - 16
DP  - 2017 Jun 1
TI  - Complete Hematologic and Molecular Response in Adult Patients With 
      Relapsed/Refractory Philadelphia Chromosome-Positive B-Precursor Acute 
      Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a 
      Phase II, Single-Arm, Multicenter Study.
PG  - 1795-1802
LID - 10.1200/JCO.2016.69.3531 [doi]
AB  - Purpose Few therapeutic options are available for patients with Philadelphia 
      chromosome-positive (Ph(+)) B-precursor acute lymphoblastic leukemia (ALL) who 
      progress after failure of tyrosine kinase inhibitor (TKI) -based therapy. Here, 
      we evaluated the efficacy and tolerability of blinatumomab in patients with 
      relapsed or refractory Ph(+) ALL. Patients and Methods This open-label phase II 
      study enrolled adults with Ph(+) ALL who had relapsed after or were refractory to 
      at least one second-generation or later TKI or were intolerant to 
      second-generation or later TKIs and intolerant or refractory to imatinib. 
      Blinatumomab was administered in 28-day cycles by continuous intravenous 
      infusion. The primary end point was complete remission (CR) or CR with partial 
      hematologic recovery (CRh) during the first two cycles. Major secondary end 
      points included minimal residual disease response, rate of allogeneic 
      hematopoietic stem-cell transplantation, relapse-free survival, overall survival, 
      and adverse events (AEs). Results Of 45 patients, 16 (36%; 95% CI, 22% to 51%) 
      achieved CR/CRh during the first two cycles, including four of 10 patients with 
      the T315I mutation; 88% of CR/CRh responders achieved a complete minimal residual 
      disease response. Seven responders (44%) proceeded to allogeneic hematopoietic 
      stem-cell transplantation, including 55% (six of 11) of transplantation-naive 
      responders. Median relapse-free survival and overall survival were 6.7 and 7.1 
      months, respectively. The most frequent AEs were pyrexia (58%), febrile 
      neutropenia (40%), and headache (31%). Three patients had cytokine release 
      syndrome (all grade 1 or 2), and three patients had grade 3 neurologic events, 
      one of which (aphasia) required temporary treatment interruption. There were no 
      grade 4 or 5 neurologic events. Conclusion Single-agent blinatumomab showed 
      antileukemia activity in high-risk patients with Ph(+) ALL who had relapsed or 
      were refractory to TKIs. AEs were consistent with previous experience in Ph(-) 
      ALL.
FAU - Martinelli, Giovanni
AU  - Martinelli G
AD  - Giovanni Martinelli and Cristina Papayannidis, Institute of Hematology and 
      Medical Oncology "L. and A. Seragnoli", Bologna; Alessandro Rambaldi, University 
      of Milan Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa 
      Giovanni XXIII, Bergamo, Italy; Nicolas Boissel, University Paris Diderot, 
      Hopital Saint-Louis, Paris; Patrice Chevallier, Centre Hospitalier Universitaire 
      Nantes, Nantes, France; Oliver Ottmann, Cardiff University, Cardiff; Adele K. 
      Fielding, University College London Cancer Institute, London, United Kingdom; 
      Nicola Gokbuget, University Hospital, Goethe University, Frankfurt; Max S. Topp, 
      Universitatsklinikum Wurzburg, Wurzburg, Germany; Ellen K. Ritchie, Weill Cornell 
      Medical College and New York Presbyterian Hospital, New York, NY; Lulu Ren 
      Sterling, Amgen, San Francisco; Jonathan Benjamin, Amgen, Thousand Oaks; and 
      Anthony Stein, Gehr Family Center for Leukemia Research, City of Hope, Duarte, 
      CA.
FAU - Boissel, Nicolas
AU  - Boissel N
AD  - Giovanni Martinelli and Cristina Papayannidis, Institute of Hematology and 
      Medical Oncology "L. and A. Seragnoli", Bologna; Alessandro Rambaldi, University 
      of Milan Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa 
      Giovanni XXIII, Bergamo, Italy; Nicolas Boissel, University Paris Diderot, 
      Hopital Saint-Louis, Paris; Patrice Chevallier, Centre Hospitalier Universitaire 
      Nantes, Nantes, France; Oliver Ottmann, Cardiff University, Cardiff; Adele K. 
      Fielding, University College London Cancer Institute, London, United Kingdom; 
      Nicola Gokbuget, University Hospital, Goethe University, Frankfurt; Max S. Topp, 
      Universitatsklinikum Wurzburg, Wurzburg, Germany; Ellen K. Ritchie, Weill Cornell 
      Medical College and New York Presbyterian Hospital, New York, NY; Lulu Ren 
      Sterling, Amgen, San Francisco; Jonathan Benjamin, Amgen, Thousand Oaks; and 
      Anthony Stein, Gehr Family Center for Leukemia Research, City of Hope, Duarte, 
      CA.
FAU - Chevallier, Patrice
AU  - Chevallier P
AD  - Giovanni Martinelli and Cristina Papayannidis, Institute of Hematology and 
      Medical Oncology "L. and A. Seragnoli", Bologna; Alessandro Rambaldi, University 
      of Milan Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa 
      Giovanni XXIII, Bergamo, Italy; Nicolas Boissel, University Paris Diderot, 
      Hopital Saint-Louis, Paris; Patrice Chevallier, Centre Hospitalier Universitaire 
      Nantes, Nantes, France; Oliver Ottmann, Cardiff University, Cardiff; Adele K. 
      Fielding, University College London Cancer Institute, London, United Kingdom; 
      Nicola Gokbuget, University Hospital, Goethe University, Frankfurt; Max S. Topp, 
      Universitatsklinikum Wurzburg, Wurzburg, Germany; Ellen K. Ritchie, Weill Cornell 
      Medical College and New York Presbyterian Hospital, New York, NY; Lulu Ren 
      Sterling, Amgen, San Francisco; Jonathan Benjamin, Amgen, Thousand Oaks; and 
      Anthony Stein, Gehr Family Center for Leukemia Research, City of Hope, Duarte, 
      CA.
FAU - Ottmann, Oliver
AU  - Ottmann O
AD  - Giovanni Martinelli and Cristina Papayannidis, Institute of Hematology and 
      Medical Oncology "L. and A. Seragnoli", Bologna; Alessandro Rambaldi, University 
      of Milan Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa 
      Giovanni XXIII, Bergamo, Italy; Nicolas Boissel, University Paris Diderot, 
      Hopital Saint-Louis, Paris; Patrice Chevallier, Centre Hospitalier Universitaire 
      Nantes, Nantes, France; Oliver Ottmann, Cardiff University, Cardiff; Adele K. 
      Fielding, University College London Cancer Institute, London, United Kingdom; 
      Nicola Gokbuget, University Hospital, Goethe University, Frankfurt; Max S. Topp, 
      Universitatsklinikum Wurzburg, Wurzburg, Germany; Ellen K. Ritchie, Weill Cornell 
      Medical College and New York Presbyterian Hospital, New York, NY; Lulu Ren 
      Sterling, Amgen, San Francisco; Jonathan Benjamin, Amgen, Thousand Oaks; and 
      Anthony Stein, Gehr Family Center for Leukemia Research, City of Hope, Duarte, 
      CA.
FAU - Gokbuget, Nicola
AU  - Gokbuget N
AD  - Giovanni Martinelli and Cristina Papayannidis, Institute of Hematology and 
      Medical Oncology "L. and A. Seragnoli", Bologna; Alessandro Rambaldi, University 
      of Milan Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa 
      Giovanni XXIII, Bergamo, Italy; Nicolas Boissel, University Paris Diderot, 
      Hopital Saint-Louis, Paris; Patrice Chevallier, Centre Hospitalier Universitaire 
      Nantes, Nantes, France; Oliver Ottmann, Cardiff University, Cardiff; Adele K. 
      Fielding, University College London Cancer Institute, London, United Kingdom; 
      Nicola Gokbuget, University Hospital, Goethe University, Frankfurt; Max S. Topp, 
      Universitatsklinikum Wurzburg, Wurzburg, Germany; Ellen K. Ritchie, Weill Cornell 
      Medical College and New York Presbyterian Hospital, New York, NY; Lulu Ren 
      Sterling, Amgen, San Francisco; Jonathan Benjamin, Amgen, Thousand Oaks; and 
      Anthony Stein, Gehr Family Center for Leukemia Research, City of Hope, Duarte, 
      CA.
FAU - Topp, Max S
AU  - Topp MS
AD  - Giovanni Martinelli and Cristina Papayannidis, Institute of Hematology and 
      Medical Oncology "L. and A. Seragnoli", Bologna; Alessandro Rambaldi, University 
      of Milan Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa 
      Giovanni XXIII, Bergamo, Italy; Nicolas Boissel, University Paris Diderot, 
      Hopital Saint-Louis, Paris; Patrice Chevallier, Centre Hospitalier Universitaire 
      Nantes, Nantes, France; Oliver Ottmann, Cardiff University, Cardiff; Adele K. 
      Fielding, University College London Cancer Institute, London, United Kingdom; 
      Nicola Gokbuget, University Hospital, Goethe University, Frankfurt; Max S. Topp, 
      Universitatsklinikum Wurzburg, Wurzburg, Germany; Ellen K. Ritchie, Weill Cornell 
      Medical College and New York Presbyterian Hospital, New York, NY; Lulu Ren 
      Sterling, Amgen, San Francisco; Jonathan Benjamin, Amgen, Thousand Oaks; and 
      Anthony Stein, Gehr Family Center for Leukemia Research, City of Hope, Duarte, 
      CA.
FAU - Fielding, Adele K
AU  - Fielding AK
AD  - Giovanni Martinelli and Cristina Papayannidis, Institute of Hematology and 
      Medical Oncology "L. and A. Seragnoli", Bologna; Alessandro Rambaldi, University 
      of Milan Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa 
      Giovanni XXIII, Bergamo, Italy; Nicolas Boissel, University Paris Diderot, 
      Hopital Saint-Louis, Paris; Patrice Chevallier, Centre Hospitalier Universitaire 
      Nantes, Nantes, France; Oliver Ottmann, Cardiff University, Cardiff; Adele K. 
      Fielding, University College London Cancer Institute, London, United Kingdom; 
      Nicola Gokbuget, University Hospital, Goethe University, Frankfurt; Max S. Topp, 
      Universitatsklinikum Wurzburg, Wurzburg, Germany; Ellen K. Ritchie, Weill Cornell 
      Medical College and New York Presbyterian Hospital, New York, NY; Lulu Ren 
      Sterling, Amgen, San Francisco; Jonathan Benjamin, Amgen, Thousand Oaks; and 
      Anthony Stein, Gehr Family Center for Leukemia Research, City of Hope, Duarte, 
      CA.
FAU - Rambaldi, Alessandro
AU  - Rambaldi A
AD  - Giovanni Martinelli and Cristina Papayannidis, Institute of Hematology and 
      Medical Oncology "L. and A. Seragnoli", Bologna; Alessandro Rambaldi, University 
      of Milan Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa 
      Giovanni XXIII, Bergamo, Italy; Nicolas Boissel, University Paris Diderot, 
      Hopital Saint-Louis, Paris; Patrice Chevallier, Centre Hospitalier Universitaire 
      Nantes, Nantes, France; Oliver Ottmann, Cardiff University, Cardiff; Adele K. 
      Fielding, University College London Cancer Institute, London, United Kingdom; 
      Nicola Gokbuget, University Hospital, Goethe University, Frankfurt; Max S. Topp, 
      Universitatsklinikum Wurzburg, Wurzburg, Germany; Ellen K. Ritchie, Weill Cornell 
      Medical College and New York Presbyterian Hospital, New York, NY; Lulu Ren 
      Sterling, Amgen, San Francisco; Jonathan Benjamin, Amgen, Thousand Oaks; and 
      Anthony Stein, Gehr Family Center for Leukemia Research, City of Hope, Duarte, 
      CA.
FAU - Ritchie, Ellen K
AU  - Ritchie EK
AD  - Giovanni Martinelli and Cristina Papayannidis, Institute of Hematology and 
      Medical Oncology "L. and A. Seragnoli", Bologna; Alessandro Rambaldi, University 
      of Milan Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa 
      Giovanni XXIII, Bergamo, Italy; Nicolas Boissel, University Paris Diderot, 
      Hopital Saint-Louis, Paris; Patrice Chevallier, Centre Hospitalier Universitaire 
      Nantes, Nantes, France; Oliver Ottmann, Cardiff University, Cardiff; Adele K. 
      Fielding, University College London Cancer Institute, London, United Kingdom; 
      Nicola Gokbuget, University Hospital, Goethe University, Frankfurt; Max S. Topp, 
      Universitatsklinikum Wurzburg, Wurzburg, Germany; Ellen K. Ritchie, Weill Cornell 
      Medical College and New York Presbyterian Hospital, New York, NY; Lulu Ren 
      Sterling, Amgen, San Francisco; Jonathan Benjamin, Amgen, Thousand Oaks; and 
      Anthony Stein, Gehr Family Center for Leukemia Research, City of Hope, Duarte, 
      CA.
FAU - Papayannidis, Cristina
AU  - Papayannidis C
AD  - Giovanni Martinelli and Cristina Papayannidis, Institute of Hematology and 
      Medical Oncology "L. and A. Seragnoli", Bologna; Alessandro Rambaldi, University 
      of Milan Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa 
      Giovanni XXIII, Bergamo, Italy; Nicolas Boissel, University Paris Diderot, 
      Hopital Saint-Louis, Paris; Patrice Chevallier, Centre Hospitalier Universitaire 
      Nantes, Nantes, France; Oliver Ottmann, Cardiff University, Cardiff; Adele K. 
      Fielding, University College London Cancer Institute, London, United Kingdom; 
      Nicola Gokbuget, University Hospital, Goethe University, Frankfurt; Max S. Topp, 
      Universitatsklinikum Wurzburg, Wurzburg, Germany; Ellen K. Ritchie, Weill Cornell 
      Medical College and New York Presbyterian Hospital, New York, NY; Lulu Ren 
      Sterling, Amgen, San Francisco; Jonathan Benjamin, Amgen, Thousand Oaks; and 
      Anthony Stein, Gehr Family Center for Leukemia Research, City of Hope, Duarte, 
      CA.
FAU - Sterling, Lulu Ren
AU  - Sterling LR
AD  - Giovanni Martinelli and Cristina Papayannidis, Institute of Hematology and 
      Medical Oncology "L. and A. Seragnoli", Bologna; Alessandro Rambaldi, University 
      of Milan Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa 
      Giovanni XXIII, Bergamo, Italy; Nicolas Boissel, University Paris Diderot, 
      Hopital Saint-Louis, Paris; Patrice Chevallier, Centre Hospitalier Universitaire 
      Nantes, Nantes, France; Oliver Ottmann, Cardiff University, Cardiff; Adele K. 
      Fielding, University College London Cancer Institute, London, United Kingdom; 
      Nicola Gokbuget, University Hospital, Goethe University, Frankfurt; Max S. Topp, 
      Universitatsklinikum Wurzburg, Wurzburg, Germany; Ellen K. Ritchie, Weill Cornell 
      Medical College and New York Presbyterian Hospital, New York, NY; Lulu Ren 
      Sterling, Amgen, San Francisco; Jonathan Benjamin, Amgen, Thousand Oaks; and 
      Anthony Stein, Gehr Family Center for Leukemia Research, City of Hope, Duarte, 
      CA.
FAU - Benjamin, Jonathan
AU  - Benjamin J
AD  - Giovanni Martinelli and Cristina Papayannidis, Institute of Hematology and 
      Medical Oncology "L. and A. Seragnoli", Bologna; Alessandro Rambaldi, University 
      of Milan Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa 
      Giovanni XXIII, Bergamo, Italy; Nicolas Boissel, University Paris Diderot, 
      Hopital Saint-Louis, Paris; Patrice Chevallier, Centre Hospitalier Universitaire 
      Nantes, Nantes, France; Oliver Ottmann, Cardiff University, Cardiff; Adele K. 
      Fielding, University College London Cancer Institute, London, United Kingdom; 
      Nicola Gokbuget, University Hospital, Goethe University, Frankfurt; Max S. Topp, 
      Universitatsklinikum Wurzburg, Wurzburg, Germany; Ellen K. Ritchie, Weill Cornell 
      Medical College and New York Presbyterian Hospital, New York, NY; Lulu Ren 
      Sterling, Amgen, San Francisco; Jonathan Benjamin, Amgen, Thousand Oaks; and 
      Anthony Stein, Gehr Family Center for Leukemia Research, City of Hope, Duarte, 
      CA.
FAU - Stein, Anthony
AU  - Stein A
AD  - Giovanni Martinelli and Cristina Papayannidis, Institute of Hematology and 
      Medical Oncology "L. and A. Seragnoli", Bologna; Alessandro Rambaldi, University 
      of Milan Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa 
      Giovanni XXIII, Bergamo, Italy; Nicolas Boissel, University Paris Diderot, 
      Hopital Saint-Louis, Paris; Patrice Chevallier, Centre Hospitalier Universitaire 
      Nantes, Nantes, France; Oliver Ottmann, Cardiff University, Cardiff; Adele K. 
      Fielding, University College London Cancer Institute, London, United Kingdom; 
      Nicola Gokbuget, University Hospital, Goethe University, Frankfurt; Max S. Topp, 
      Universitatsklinikum Wurzburg, Wurzburg, Germany; Ellen K. Ritchie, Weill Cornell 
      Medical College and New York Presbyterian Hospital, New York, NY; Lulu Ren 
      Sterling, Amgen, San Francisco; Jonathan Benjamin, Amgen, Thousand Oaks; and 
      Anthony Stein, Gehr Family Center for Leukemia Research, City of Hope, Duarte, 
      CA.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20170329
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibodies, Bispecific)
RN  - 0 (Antineoplastic Agents)
RN  - 4FR53SIF3A (blinatumomab)
SB  - IM
EIN - J Clin Oncol. 2017 Aug 10;35(23):2722. PMID: 28783483
EIN - J Clin Oncol. 2017 Aug 20;35(24):2856. PMID: 28813637
MH  - Adult
MH  - Antibodies, Bispecific/*therapeutic use
MH  - Antineoplastic Agents/*therapeutic use
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Middle Aged
MH  - Philadelphia Chromosome
MH  - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy
MH  - Young Adult
EDAT- 2017/03/30 06:00
MHDA- 2017/09/14 06:00
CRDT- 2017/03/30 06:00
PHST- 2017/03/30 06:00 [pubmed]
PHST- 2017/09/14 06:00 [medline]
PHST- 2017/03/30 06:00 [entrez]
AID - 10.1200/JCO.2016.69.3531 [doi]
PST - ppublish
SO  - J Clin Oncol. 2017 Jun 1;35(16):1795-1802. doi: 10.1200/JCO.2016.69.3531. Epub 
      2017 Mar 29.