Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia

Hagop M Kantarjian, Anthony Stein, Nicola Gökbuget, Adele K. Fielding, Andre C. Schuh, Josep Maria Ribera, Andrew Wei, Hervé Dombret, Robin Foà, Renato Bassan, Önder Arslan, Miguel A. Sanz, Julie Bergeron, Fatih Demirkan, Ewa Lech-Maranda, Alessandro Rambaldi, Xavier Thomas, Heinz-August Horst, Monika Brüggemann, Wolfram Klapper & 6 others Brent L. Wood, Alex Fleishman, Dirk Nagorsen, Christopher J. Holland, Zachary Zimmerman, Max S. Topp

Research output: Contribution to journalArticleResearchpeer-review

Abstract

BACKGROUND Blinatumomab, a bispecific monoclonal antibody construct that enables CD3-positive T cells to recognize and eliminate CD19-positive acute lymphoblastic leukemia (ALL) blasts, was approved for use in patients with relapsed or refractory B-cell precursor ALL on the basis of single-group trials that showed efficacy and manageable toxic effects. METHODS In this multi-institutional phase 3 trial, we randomly assigned adults with heavily pretreated B-cell precursor ALL, in a 2:1 ratio, to receive either blinatumomab or standardof-care chemotherapy. The primary end point was overall survival. RESULTS Of the 405 patients who were randomly assigned to receive blinatumomab (271 patients) or chemotherapy (134 patients), 376 patients received at least one dose. Overall survival was significantly longer in the blinatumomab group than in the chemotherapy group. The median overall survival was 7.7 months in the blinatumomab group and 4.0 months in the chemotherapy group (hazard ratio for death with blinatumomab vs. chemotherapy, 0.71; 95% confidence interval [CI], 0.55 to 0.93; P = 0.01). Remission rates within 12 weeks after treatment initiation were significantly higher in the blinatumomab group than in the chemotherapy group, both with respect to complete remission with full hematologic recovery (34% vs. 16%, P<0.001) and with respect to complete remission with full, partial, or incomplete hematologic recovery (44% vs. 25%, P<0.001). Treatment with blinatumomab resulted in a higher rate of event-free survival than that with chemotherapy (6-month estimates, 31% vs. 12%; hazard ratio for an event of relapse after achieving a complete remission with full, partial, or incomplete hematologic recovery, or death, 0.55; 95% CI, 0.43 to 0.71; P<0.001), as well as a longer median duration of remission (7.3 vs. 4.6 months). A total of 24% of the patients in each treatment group underwent allogeneic stem-cell transplantation. Adverse events of grade 3 or higher were reported in 87% of the patients in the blinatumomab group and in 92% of the patients in the chemotherapy group. CONCLUSIONS Treatment with blinatumomab resulted in significantly longer overall survival than chemotherapy among adult patients with relapsed or refractory B-cell precursor ALL.

Original languageEnglish
Pages (from-to)836-847
Number of pages12
JournalNew England Journal of Medicine
Volume376
Issue number9
DOIs
Publication statusPublished - 2 Mar 2017

Cite this

Kantarjian, H. M., Stein, A., Gökbuget, N., Fielding, A. K., Schuh, A. C., Ribera, J. M., ... Topp, M. S. (2017). Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. New England Journal of Medicine, 376(9), 836-847. https://doi.org/10.1056/NEJMoa1609783
Kantarjian, Hagop M ; Stein, Anthony ; Gökbuget, Nicola ; Fielding, Adele K. ; Schuh, Andre C. ; Ribera, Josep Maria ; Wei, Andrew ; Dombret, Hervé ; Foà, Robin ; Bassan, Renato ; Arslan, Önder ; Sanz, Miguel A. ; Bergeron, Julie ; Demirkan, Fatih ; Lech-Maranda, Ewa ; Rambaldi, Alessandro ; Thomas, Xavier ; Horst, Heinz-August ; Brüggemann, Monika ; Klapper, Wolfram ; Wood, Brent L. ; Fleishman, Alex ; Nagorsen, Dirk ; Holland, Christopher J. ; Zimmerman, Zachary ; Topp, Max S. / Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. In: New England Journal of Medicine. 2017 ; Vol. 376, No. 9. pp. 836-847.
@article{21956689a2934b1084351ca62f7890f0,
title = "Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia",
abstract = "BACKGROUND Blinatumomab, a bispecific monoclonal antibody construct that enables CD3-positive T cells to recognize and eliminate CD19-positive acute lymphoblastic leukemia (ALL) blasts, was approved for use in patients with relapsed or refractory B-cell precursor ALL on the basis of single-group trials that showed efficacy and manageable toxic effects. METHODS In this multi-institutional phase 3 trial, we randomly assigned adults with heavily pretreated B-cell precursor ALL, in a 2:1 ratio, to receive either blinatumomab or standardof-care chemotherapy. The primary end point was overall survival. RESULTS Of the 405 patients who were randomly assigned to receive blinatumomab (271 patients) or chemotherapy (134 patients), 376 patients received at least one dose. Overall survival was significantly longer in the blinatumomab group than in the chemotherapy group. The median overall survival was 7.7 months in the blinatumomab group and 4.0 months in the chemotherapy group (hazard ratio for death with blinatumomab vs. chemotherapy, 0.71; 95{\%} confidence interval [CI], 0.55 to 0.93; P = 0.01). Remission rates within 12 weeks after treatment initiation were significantly higher in the blinatumomab group than in the chemotherapy group, both with respect to complete remission with full hematologic recovery (34{\%} vs. 16{\%}, P<0.001) and with respect to complete remission with full, partial, or incomplete hematologic recovery (44{\%} vs. 25{\%}, P<0.001). Treatment with blinatumomab resulted in a higher rate of event-free survival than that with chemotherapy (6-month estimates, 31{\%} vs. 12{\%}; hazard ratio for an event of relapse after achieving a complete remission with full, partial, or incomplete hematologic recovery, or death, 0.55; 95{\%} CI, 0.43 to 0.71; P<0.001), as well as a longer median duration of remission (7.3 vs. 4.6 months). A total of 24{\%} of the patients in each treatment group underwent allogeneic stem-cell transplantation. Adverse events of grade 3 or higher were reported in 87{\%} of the patients in the blinatumomab group and in 92{\%} of the patients in the chemotherapy group. CONCLUSIONS Treatment with blinatumomab resulted in significantly longer overall survival than chemotherapy among adult patients with relapsed or refractory B-cell precursor ALL.",
author = "Kantarjian, {Hagop M} and Anthony Stein and Nicola G{\"o}kbuget and Fielding, {Adele K.} and Schuh, {Andre C.} and Ribera, {Josep Maria} and Andrew Wei and Herv{\'e} Dombret and Robin Fo{\`a} and Renato Bassan and {\"O}nder Arslan and Sanz, {Miguel A.} and Julie Bergeron and Fatih Demirkan and Ewa Lech-Maranda and Alessandro Rambaldi and Xavier Thomas and Heinz-August Horst and Monika Br{\"u}ggemann and Wolfram Klapper and Wood, {Brent L.} and Alex Fleishman and Dirk Nagorsen and Holland, {Christopher J.} and Zachary Zimmerman and Topp, {Max S.}",
year = "2017",
month = "3",
day = "2",
doi = "10.1056/NEJMoa1609783",
language = "English",
volume = "376",
pages = "836--847",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachusetts Medical Society",
number = "9",

}

Kantarjian, HM, Stein, A, Gökbuget, N, Fielding, AK, Schuh, AC, Ribera, JM, Wei, A, Dombret, H, Foà, R, Bassan, R, Arslan, Ö, Sanz, MA, Bergeron, J, Demirkan, F, Lech-Maranda, E, Rambaldi, A, Thomas, X, Horst, H-A, Brüggemann, M, Klapper, W, Wood, BL, Fleishman, A, Nagorsen, D, Holland, CJ, Zimmerman, Z & Topp, MS 2017, 'Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia', New England Journal of Medicine, vol. 376, no. 9, pp. 836-847. https://doi.org/10.1056/NEJMoa1609783

Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. / Kantarjian, Hagop M; Stein, Anthony; Gökbuget, Nicola; Fielding, Adele K.; Schuh, Andre C.; Ribera, Josep Maria; Wei, Andrew; Dombret, Hervé; Foà, Robin; Bassan, Renato; Arslan, Önder; Sanz, Miguel A.; Bergeron, Julie; Demirkan, Fatih; Lech-Maranda, Ewa; Rambaldi, Alessandro; Thomas, Xavier; Horst, Heinz-August; Brüggemann, Monika; Klapper, Wolfram; Wood, Brent L.; Fleishman, Alex; Nagorsen, Dirk; Holland, Christopher J.; Zimmerman, Zachary; Topp, Max S.

In: New England Journal of Medicine, Vol. 376, No. 9, 02.03.2017, p. 836-847.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia

AU - Kantarjian, Hagop M

AU - Stein, Anthony

AU - Gökbuget, Nicola

AU - Fielding, Adele K.

AU - Schuh, Andre C.

AU - Ribera, Josep Maria

AU - Wei, Andrew

AU - Dombret, Hervé

AU - Foà, Robin

AU - Bassan, Renato

AU - Arslan, Önder

AU - Sanz, Miguel A.

AU - Bergeron, Julie

AU - Demirkan, Fatih

AU - Lech-Maranda, Ewa

AU - Rambaldi, Alessandro

AU - Thomas, Xavier

AU - Horst, Heinz-August

AU - Brüggemann, Monika

AU - Klapper, Wolfram

AU - Wood, Brent L.

AU - Fleishman, Alex

AU - Nagorsen, Dirk

AU - Holland, Christopher J.

AU - Zimmerman, Zachary

AU - Topp, Max S.

PY - 2017/3/2

Y1 - 2017/3/2

N2 - BACKGROUND Blinatumomab, a bispecific monoclonal antibody construct that enables CD3-positive T cells to recognize and eliminate CD19-positive acute lymphoblastic leukemia (ALL) blasts, was approved for use in patients with relapsed or refractory B-cell precursor ALL on the basis of single-group trials that showed efficacy and manageable toxic effects. METHODS In this multi-institutional phase 3 trial, we randomly assigned adults with heavily pretreated B-cell precursor ALL, in a 2:1 ratio, to receive either blinatumomab or standardof-care chemotherapy. The primary end point was overall survival. RESULTS Of the 405 patients who were randomly assigned to receive blinatumomab (271 patients) or chemotherapy (134 patients), 376 patients received at least one dose. Overall survival was significantly longer in the blinatumomab group than in the chemotherapy group. The median overall survival was 7.7 months in the blinatumomab group and 4.0 months in the chemotherapy group (hazard ratio for death with blinatumomab vs. chemotherapy, 0.71; 95% confidence interval [CI], 0.55 to 0.93; P = 0.01). Remission rates within 12 weeks after treatment initiation were significantly higher in the blinatumomab group than in the chemotherapy group, both with respect to complete remission with full hematologic recovery (34% vs. 16%, P<0.001) and with respect to complete remission with full, partial, or incomplete hematologic recovery (44% vs. 25%, P<0.001). Treatment with blinatumomab resulted in a higher rate of event-free survival than that with chemotherapy (6-month estimates, 31% vs. 12%; hazard ratio for an event of relapse after achieving a complete remission with full, partial, or incomplete hematologic recovery, or death, 0.55; 95% CI, 0.43 to 0.71; P<0.001), as well as a longer median duration of remission (7.3 vs. 4.6 months). A total of 24% of the patients in each treatment group underwent allogeneic stem-cell transplantation. Adverse events of grade 3 or higher were reported in 87% of the patients in the blinatumomab group and in 92% of the patients in the chemotherapy group. CONCLUSIONS Treatment with blinatumomab resulted in significantly longer overall survival than chemotherapy among adult patients with relapsed or refractory B-cell precursor ALL.

AB - BACKGROUND Blinatumomab, a bispecific monoclonal antibody construct that enables CD3-positive T cells to recognize and eliminate CD19-positive acute lymphoblastic leukemia (ALL) blasts, was approved for use in patients with relapsed or refractory B-cell precursor ALL on the basis of single-group trials that showed efficacy and manageable toxic effects. METHODS In this multi-institutional phase 3 trial, we randomly assigned adults with heavily pretreated B-cell precursor ALL, in a 2:1 ratio, to receive either blinatumomab or standardof-care chemotherapy. The primary end point was overall survival. RESULTS Of the 405 patients who were randomly assigned to receive blinatumomab (271 patients) or chemotherapy (134 patients), 376 patients received at least one dose. Overall survival was significantly longer in the blinatumomab group than in the chemotherapy group. The median overall survival was 7.7 months in the blinatumomab group and 4.0 months in the chemotherapy group (hazard ratio for death with blinatumomab vs. chemotherapy, 0.71; 95% confidence interval [CI], 0.55 to 0.93; P = 0.01). Remission rates within 12 weeks after treatment initiation were significantly higher in the blinatumomab group than in the chemotherapy group, both with respect to complete remission with full hematologic recovery (34% vs. 16%, P<0.001) and with respect to complete remission with full, partial, or incomplete hematologic recovery (44% vs. 25%, P<0.001). Treatment with blinatumomab resulted in a higher rate of event-free survival than that with chemotherapy (6-month estimates, 31% vs. 12%; hazard ratio for an event of relapse after achieving a complete remission with full, partial, or incomplete hematologic recovery, or death, 0.55; 95% CI, 0.43 to 0.71; P<0.001), as well as a longer median duration of remission (7.3 vs. 4.6 months). A total of 24% of the patients in each treatment group underwent allogeneic stem-cell transplantation. Adverse events of grade 3 or higher were reported in 87% of the patients in the blinatumomab group and in 92% of the patients in the chemotherapy group. CONCLUSIONS Treatment with blinatumomab resulted in significantly longer overall survival than chemotherapy among adult patients with relapsed or refractory B-cell precursor ALL.

UR - http://www.scopus.com/inward/record.url?scp=85014771892&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1609783

DO - 10.1056/NEJMoa1609783

M3 - Article

VL - 376

SP - 836

EP - 847

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 9

ER -

Kantarjian HM, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera JM et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. New England Journal of Medicine. 2017 Mar 2;376(9):836-847. https://doi.org/10.1056/NEJMoa1609783