TY - JOUR
T1 - Long-term follow-up of salvage therapy using a combination of inotuzumab ozogamicin and mini–hyper-CVD with or without blinatumomab in relapsed/refractory Philadelphia chromosome–negative acute lymphoblastic leukemia
AU - Jabbour, Elias
AU - Sasaki, Koji
AU - Short, Nicholas J.
AU - Ravandi, Farhad
AU - Huang, Xuelin
AU - Khoury, Joseph D.
AU - Kanagal-Shamanna, Rashmi
AU - Jorgensen, Jeffrey
AU - Khouri, Issa F.
AU - Kebriaei, Partow
AU - Jain, Nitin
AU - Alvarado, Yesid
AU - Kadia, Tapan M.
AU - Paul, Shilpa
AU - Garcia-Manero, Guillermo
AU - Dabaja, Bouthaina S.
AU - Burger, Jan A.
AU - DiNardo, Courtney D.
AU - Daver, Naval A.
AU - Montalban-Bravo, Guillermo
AU - Yilmaz, Musa
AU - Ohanian, Maro
AU - Ferrajoli, Alessandra
AU - Jacob, Jovitta
AU - Rostykus, Meagan
AU - Garris, Rebecca
AU - O’Brien, Susan
AU - Kantarjian, Hagop M.
N1 - Funding Information:
The original clinical trial was supported by research funding from Pfizer and Amgen.
Funding Information:
Elias Jabbour has received research funding from AbbVie, Adaptive, Amgen, BMS, Cyclacel LTD, Pfizer, and Takeda Oncology and has been a consultant for AbbVie, Adaptive, Amgen, BMS, Pfizer, and Takeda Oncology. Koji Sasaki has received research funding from Novartis, has been a consultant for Daiichi Sankyo and Pfizer, and has received honoraria from Otsuka. Nicholas J. Short has received research funding from Astellas and Takeda Oncology, has been a consultant for AstraZeneca and Takeda Oncology, and has received honoraria from Amgen and AstraZeneca. Farhad Ravandi has received research funding from Amgen, Cyclacel LTD, Macrogenix, Menarini Ricerche, Selvita, and Xencor; has been a consultant for Macrogenix and Xencor; has received honoraria from Amgen; and has served on the Board of Directors for Amgen. Joseph D. Khoury has received research funding from Angle, Kiromic, and Stemline Therapeutics. Issa F. Khouri has received research funding from Bristol Myers Squibb and Pfizer. Partow Kebriaei has received research funding from Amgen and has been a consultant for Pfizer. Nitin Jain has received research funding from AbbVie, Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, Bristol Myers Squibb, Cellectis, Genentech, Incyte, Pfizer, Pharmacyclics, Precision Biosciences, Servier, and Verastem; has been a consultant for AbbVie, Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, Genentech, Janssen Pharmaceuticals, Pfizer, Pharmacyclics, Precision Biosciences, Servier, and Verastem; has received honoraria from AbbVie, Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, Genentech, Janssen Pharmaceuticals, Pfizer, Pharmacyclics, Precision Biosciences, Servier, and Verastem; and has served on the Board of Directors or advisory committee for AbbVie, Adaptive Biotechnologies, ADC Therapeutics, AstraZeneca, Genentech, Janssen Pharmaceuticals, Pfizer, Pharmacyclics, Precision Biosciences, Servier, and Verastem. Yesid Alvarado has received research funding from Jazz Pharmaceuticals and has received honoraria from Abbott. Tapan M. Kadia has received research funding from AbbVie, Amgen, Bioline RX, Bristol Myers Squibb, Celgene, Jazz Pharmaceuticals, and Pfizer; has been a consultant for AbbVie; and has served on the Board of Directors or advisory committee for Amgen, Genentech, Jazz Pharmaceuticals, Pfizer, Pharmacyclics, and Takeda Oncology. Guillermo Garcia‐Manero has received research funding from AbbVie, Amphivena, Astex, Celgene, H3 Biomedicine, Helsinn, Merck, Novartis, and Onconova and has been a consultant for Amphivena, Astex, and Celgene. Jan A. Burger has received research funding from Aptose Biosciences, BeiGene, Gilead Sciences, Pharmacyclics, and TG Therapeutics; has been a consultant for Janssen Pharmaceuticals; has received honoraria from AstraZeneca, Gilead Sciences, Janssen Pharmaceuticals, Novartis, Pharmacyclics, and TG Therapeutics; and has served on speakers bureaus for Gilead Sciences, Janssen Pharmaceuticals, Novartis, Pharmacyclics, and TG Therapeutics. Courtney D. DiNardo has received research funding from AbbVie, Agios, Bristol Myers Squibb, Calithera, Celgene, Daiichi Sankyo, ImmuneOnc, and Novartis; has been a consultant for AbbVie, Agios, and Celgene; has received honoraria from AbbVie, Agios, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Foghorn, ImmuneOnc, Jazz Pharmaceuticals, MedImmune, Notable Labs, Novartis, Syros Pharmaceuticals, and Takeda Oncology; and has served on the Board of Directors or advisory committee for Notable Labs. Naval A. Daver has received research funding from AbbVie, Affymetrix, Bristol Myers Squibb, Cellectis, Daiichi Sankyo, Genentech, Glycomimetics, Hanmi Pharmaceutical, Immunogen, Incyte, Karyopharm, MustangBio, NOHLA, Novartis, Pfizer, Plexxikon, SagerStrong, Samus Therapeutics, Servier, Stemline Therapeutics, and Sunesis; has been a consultant for AbbVie, Agios, Astellas, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Forty‐Seven, Genentech, Immunogen, Incyte, Jazz Pharmaceuticals, Karyopharm, MustangBio, Novartis, Otsuka, Pfizer, Stemline Therapeutics, and Sunesis; and has received honoraria from AbbVie, Celgene, and Stemline Therapeutics. Musa Yilmaz has received research funding from Daiichi Sankyo and Pfizer and has received honoraria from Pint Pharma. Susan O’Brien has received research funding from Acerta, Gilead, Kite, Pfizer, Pharmacyclics, Regeneron, Sunesis, and TG Therapeutics and has been a consultant for AbbVie, Alexion, Amgen, Aptose Biosciences, Astellas, Autolus, Celgene, Eisai, Gilead, GlaxoSmithKline, Janssen Oncology, Johnson & Johnson, Pfizer, Pharmacyclics, Sunesis, TG Therapeutics, Vaniam Group, Verastem, and Vida Ventures. Hagop M. Kantarjian has received research funding from AbbVie, Agios, Amgen, Ariad, Ascentage, Astex, Bristol Myers Squibb, Cyclacel, Daiichi Sankyo, Immunogen, Jazz Pharmaceuticals, Novartis, Pfizer, and Sanofi; has received honoraria from AbbVie, Actinium, Adaptive Biotechnologies, Agios, Amgen, Aptitude Health, Bio Ascend, Daiichi Sankyo, Delta Fly, Janssen Global, Novartis, Oxford Biomedical, Pfizer, and Takeda Oncology; and has served on the Board of Directors or advisory committee for Actinium. The other authors made no disclosures.
Publisher Copyright:
© 2021 American Cancer Society
PY - 2021/6/15
Y1 - 2021/6/15
N2 - BACKGROUND: The outcome of patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. The combination of inotuzumab with low-intensity mini–hyper-CVD (mini-hyper-CVD; cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 × 4 doses) chemotherapy has shown encouraging results. The sequential addition of blinatumomab might improve outcome in patients with R/R ALL. METHODS: We used lower intensity chemotherapy, mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 x 4 doses) compared to conventional hyper-CVAD. RESULTS: Ninety-six patients with a median age of 37 years (range, 18-87 years) were treated. Overall, 77 patients (80%) responded, 55 (57%) of whom achieved complete response. The overall measurable residual disease negativity rate among responders was 83%. Forty-four (46%) patients underwent later allogeneic stem cell transplantation. Veno-occlusive disease of any grade occurred in 10 (10%) patients. The rates were 13% with the original schedule and 3% with the use of lower-dose inotuzumab and sequential blinatumomab. With a median follow-up of 36 months, the median overall survival (OS) was 13.4 months, with 3-year OS rates of 33%. The 3-year OS rate for patients with CD22 expression ≥70% and without adverse cytogenetics (KMT2A rearrangements, low hypodiploidy/near triploidy) was 55%. CONCLUSION: The combination of inotuzumab and low-intensity mini-hyper-CVD chemotherapy with or without blinatumomab shows sustained efficacy in patients with R/R ALL.
AB - BACKGROUND: The outcome of patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. The combination of inotuzumab with low-intensity mini–hyper-CVD (mini-hyper-CVD; cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 × 4 doses) chemotherapy has shown encouraging results. The sequential addition of blinatumomab might improve outcome in patients with R/R ALL. METHODS: We used lower intensity chemotherapy, mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 x 4 doses) compared to conventional hyper-CVAD. RESULTS: Ninety-six patients with a median age of 37 years (range, 18-87 years) were treated. Overall, 77 patients (80%) responded, 55 (57%) of whom achieved complete response. The overall measurable residual disease negativity rate among responders was 83%. Forty-four (46%) patients underwent later allogeneic stem cell transplantation. Veno-occlusive disease of any grade occurred in 10 (10%) patients. The rates were 13% with the original schedule and 3% with the use of lower-dose inotuzumab and sequential blinatumomab. With a median follow-up of 36 months, the median overall survival (OS) was 13.4 months, with 3-year OS rates of 33%. The 3-year OS rate for patients with CD22 expression ≥70% and without adverse cytogenetics (KMT2A rearrangements, low hypodiploidy/near triploidy) was 55%. CONCLUSION: The combination of inotuzumab and low-intensity mini-hyper-CVD chemotherapy with or without blinatumomab shows sustained efficacy in patients with R/R ALL.
KW - Philadelphia-negative ALL
KW - blinatumomab
KW - chemo-immunotherapy
KW - inotuzumab
KW - outcome
KW - salvage
UR - http://www.scopus.com/inward/record.url?scp=85102705101&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85102705101&partnerID=8YFLogxK
U2 - 10.1002/cncr.33469
DO - 10.1002/cncr.33469
M3 - Article
C2 - 33740268
AN - SCOPUS:85102705101
SN - 0008-543X
VL - 127
SP - 2025
EP - 2038
JO - Cancer
JF - Cancer
IS - 12
ER -