TY - JOUR
T1 - Inotuzumab ozogamicin in combination with low-intensity chemotherapy (mini-HCVD) with or without blinatumomab versus standard intensive chemotherapy (HCVAD) as frontline therapy for older patients with Philadelphia chromosome-negative acute lymphoblastic leukemia
T2 - A propensity score analysis
AU - Jabbour, Elias J.
AU - Sasaki, Koji
AU - Ravandi, Farhad
AU - Short, Nicholas J.
AU - Garcia-Manero, Guillermo
AU - Daver, Naval
AU - Kadia, Tapan
AU - Konopleva, Marina
AU - Jain, Nitin
AU - Cortes, Jorge
AU - Issa, Ghayas C.
AU - Jacob, Jovitta
AU - Kwari, Monica
AU - Thompson, Philip
AU - Garris, Rebecca
AU - Pemmaraju, Naveen
AU - Yilmaz, Musa
AU - O’Brien, Susan M.
AU - Kantarjian, Hagop M.
N1 - Funding Information:
Elias J. Jabbour reports research funding and consultancy fees from Amgen and Pfizer outside the submitted work. Koji Sasaki reports consultancy fees from Pfizer Japan outside the submitted work. Guillermo Garcia-Manero reports research funding from Amphivena, Helsinn, Novartis, AbbVie, Celgene, Astex, Onconova, and Merck during the course of the study. Jorge Cortes reports research funding and consultancy fees from Bristol-Myers Squibb, Pfizer, and Takeda outside the submitted work. Philip Thompson reports research funding from Pfizer; research funding and consultancy fees from Amgen, AbbVie, and Pharmacyclics; and consultancy fees from Genentech, all outside the submitted work. Naveen Pemmaraju reports research funding from Affymetrix and the SagerStrong Foundation; consultancy fees from Celegene, Stemline Incyte, MustangBio, Roche Diagnostics, LFB, and Novartis; and research funding from AbbVie, Samus, Cellectis, Plexxikon, and Daiichi-Sankyo, all outside the submitted work. Hagop M. Kantarjian reports research funding from AbbVie, Agios, Amgen, Ariad, Astex, Bristol-Myers Squibb, Cyclacel, Daiichi-Sankyo, Immunogen, Jazz Pharma, Novartis, and Pfizer; and consultancy fees from AbbVie, Actinium, Agios, Amgen, Immunogen, Orsinex, Pfizer, and Takeda during the conduct of the study. The remaining authors made no disclosures.
Funding Information:
Elias J. Jabbour reports research funding and consultancy fees from Amgen and Pfizer outside the submitted work. Koji Sasaki reports consultancy fees from Pfizer Japan outside the submitted work. Guillermo Garcia-Manero reports research funding from Amphivena, Helsinn, Novartis, AbbVie, Celgene, Astex, Onconova, and Merck during the course of the study. Jorge Cortes reports research funding and consultancy fees from Bristol-Myers Squibb, Pfizer, and Takeda outside the submitted work. Philip Thompson reports research funding from Pfizer; research funding and consultancy fees from Amgen, AbbVie, and Pharmacyclics; and consultancy fees from Genentech, all outside the submitted work. Naveen Pemmaraju reports research funding from Affymetrix and the SagerStrong Foundation; consultancy fees from Celegene, Stemline Incyte, MustangBio, Roche Diagnostics, LFB, and Novartis; and research funding from AbbVie, Samus, Cellectis, Plexxikon, and Daiichi-Sankyo, all outside the submitted work. Hagop M. Kantarjian reports research funding from AbbVie, Agios, Amgen, Ariad, Astex, Bristol-Myers Squibb, Cyclacel, Daiichi-Sankyo, Immunogen, Jazz Pharma, Novartis, and Pfizer; and consultancy fees from AbbVie, Actinium, Agios, Amgen, Immunogen, Orsinex, Pfizer, and Takeda during the conduct of the study. The remaining authors made no disclosures. Pfizer provided free drug from the Pfizer Investigator Sponsored Trial program. Amgen provided free drug from the Amgen Investigator Sponsored Trial program.
Publisher Copyright:
© 2019 American Cancer Society
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Background: The outcome of older patients with newly diagnosed, Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) is poor. The combination of targeted therapy with low-intensity chemotherapy is safe and effective. The objective of the current analysis was to compare the outcome of patients who received a combination of inotuzumab ozogamicin plus low-intensity chemotherapy (mini–hyperfractionated cyclophosphamide, vincristine, and dexamethasone [mini-HCVD]) with or without blinatumomab versus the outcome of those who received the standard, intensive, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD) regimen. Methods: The authors analyzed 135 older patients with newly diagnosed, Ph-negative ALL who were treated prospectively with standard HCVAD (n = 77) or with the combination of inotuzumab ozogamicin plus mini-HCVD with or without blinatumomab (n = 58). A propensity score analysis was conducted using 1:1 matching using the nearest neighbor matching method. Results: Propensity score matching identified 38 patients in each cohort. The antibody plus low-intensity chemotherapy combination induced higher response rates (98% vs 88%), with lower rates of early death (0% vs 8%) and lower rates of death in complete remission (5% vs 17%). With propensity score matching, the 3-year event-free survival rates for patients who received HCVAD and those who received the combination of inotuzumab ozogamicin plus mini-HCVD with or without blinatumomab were 34% and 64%, respectively (P =.003), and the 3-year overall survival rates were 34% and 63%, respectively (P =.004). By multivariate analysis, age (P =.019; hazard ratio, 1.045) and the combination of inotuzumab plus mini-HCVD with or without blinatumomab (P =.020; hazard ratio, 0.550) were identified as independent prognostic factors for survival. Conclusions: The combination of inotuzumab ozogamicin plus mini-HCVD with or without blinatumomab is safe and effective in older patients with newly diagnosed, Ph-negative ALL and confers a better outcome compared with standard HCVAD chemotherapy.
AB - Background: The outcome of older patients with newly diagnosed, Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) is poor. The combination of targeted therapy with low-intensity chemotherapy is safe and effective. The objective of the current analysis was to compare the outcome of patients who received a combination of inotuzumab ozogamicin plus low-intensity chemotherapy (mini–hyperfractionated cyclophosphamide, vincristine, and dexamethasone [mini-HCVD]) with or without blinatumomab versus the outcome of those who received the standard, intensive, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD) regimen. Methods: The authors analyzed 135 older patients with newly diagnosed, Ph-negative ALL who were treated prospectively with standard HCVAD (n = 77) or with the combination of inotuzumab ozogamicin plus mini-HCVD with or without blinatumomab (n = 58). A propensity score analysis was conducted using 1:1 matching using the nearest neighbor matching method. Results: Propensity score matching identified 38 patients in each cohort. The antibody plus low-intensity chemotherapy combination induced higher response rates (98% vs 88%), with lower rates of early death (0% vs 8%) and lower rates of death in complete remission (5% vs 17%). With propensity score matching, the 3-year event-free survival rates for patients who received HCVAD and those who received the combination of inotuzumab ozogamicin plus mini-HCVD with or without blinatumomab were 34% and 64%, respectively (P =.003), and the 3-year overall survival rates were 34% and 63%, respectively (P =.004). By multivariate analysis, age (P =.019; hazard ratio, 1.045) and the combination of inotuzumab plus mini-HCVD with or without blinatumomab (P =.020; hazard ratio, 0.550) were identified as independent prognostic factors for survival. Conclusions: The combination of inotuzumab ozogamicin plus mini-HCVD with or without blinatumomab is safe and effective in older patients with newly diagnosed, Ph-negative ALL and confers a better outcome compared with standard HCVAD chemotherapy.
KW - blinatumomab
KW - inotuzumab
KW - mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone (mini-HCVD)
KW - older acute lymphoblastic leukemia (ALL)
KW - outcome
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U2 - 10.1002/cncr.32139
DO - 10.1002/cncr.32139
M3 - Article
C2 - 30985931
AN - SCOPUS:85064517337
SN - 0008-543X
VL - 125
SP - 2579
EP - 2586
JO - Cancer
JF - Cancer
IS - 15
ER -