TY - JOUR
T1 - Ten-day decitabine with venetoclax versus intensive chemotherapy in relapsed or refractory acute myeloid leukemia
T2 - A propensity score-matched analysis
AU - Maiti, Abhishek
AU - DiNardo, Courtney D.
AU - Qiao, Wei
AU - Kadia, Tapan M.
AU - Jabbour, Elias J.
AU - Rausch, Caitlin R.
AU - Daver, Naval G.
AU - Short, Nicholas J.
AU - Borthakur, Gautam
AU - Pemmaraju, Naveen
AU - Yilmaz, Musa
AU - Alvarado, Yesid
AU - Montalbano, Kathryn S.
AU - Wade, Allison
AU - Maduike, Rita E.
AU - Guerrero, Julio A.
AU - Vaughan, Kenneth
AU - Bivins, Carol A.
AU - Pierce, Sherry
AU - Ning, Jing
AU - Ravandi, Farhad
AU - Kantarjian, Hagop M.
AU - Konopleva, Marina Y.
N1 - Funding Information:
This study was supported in part by the MD Anderson Cancer Center (Support Grant CA016672) from the National Cancer Institute, and the Research Project (Grant Program R01CA235622) from the National Institutes of Health. Abhishek Maiti was supported in part by the American Society of Clinical Oncology Young Investigator Award from the Conquer Cancer Foundation.
Funding Information:
Abhishek Maiti received research funding from Celgene Corporation. Courtney D. DiNardo received personal fees from AbbVie, personal fees from Agios, Novartis, ImmuneOnc, Daiichi Sankyo, Celgene, Jazz Pharmaceuticals, and Notable Labs, from outside the submitted work. Elias J. Jabbour received consultancy research funding from Takeda, BMS, Adaptive, Amgen, AbbVie, Pfizer, and Cyclacel Ltd; and research grants with Amgen, AbbVie, Spectrum, BMS, Takeda, Pfizer, and Adaptive. Naval G. Daver reports grants from AbbVie, Genentech, Astellas, Daiichi‐Sankyo, Pfizer, BMS, Immunogen, Novimmune, and Forty‐Seven; and personal fees from AbbVie, Genentech, Astellas, Daiichi‐Sankyo, Pfizer, BMS, Immunogen, Jazz Pharmaceuticals, Trillium, Forty‐seven, Gilead, Kite, and Novartis. Nicholas J. Short reports grants from Takeda Oncology and Astellas, as well as personal fees from Takeda Oncology, AstraZeneca, and Amgen. Gautam Borthakur received research funding from AbbVie, Incyte, and Janssen. Naveen Pemmaraju reports personal fees from Pacylex Pharmaceuticals and Incyte; grants and other support from Affymetrix; grants from SagerStrong Foundation; personal fees and other support from Novartis; personal fees from LFB Biotechnologies, Roche Diagnostics, and Blueprint Medicines; personal fees, nonfinancial support, and other support from Stemline Therapeutics and AbbVie; personal fees and nonfinancial support from Celgene, MustangBio, and DAVA Oncology; other support from Samus Therapeutics, Cellectis, Daiichi Sankyo, and Plexxikon, outside the submitted work. Hagop M. Kantarjian received grants and other support from AbbVie, Agios, Amgen, Immunogen, and Pfizer; grants from Ariad, Astex, BMS, Cyclacel, Daiichi‐Sankyo, Jazz Pharmaceuticals, and Novartis; and other support from Actinium and Takeda, outside the submitted work. Farhad Ravandi received personal fees and research grants from AbbVie. Hagtop M. Kantarjian received research grants from AbbVie, Amgen, Ascentage, BMS, Daiichi‐Sankyo, Immunogen, Jazz Pharmaceuticals, Novartis, Pfizer, and Sanofi; and honoraria from AbbVie, Actinium (Advisory Board), Addaptive Biotechnologies, Amgen, Aptitude Health, BioAscend, Daiichi‐Sankyo, Delta Fly, Janssen Global, Novartis, Oxford Biomedical, Pfizer, and Takeda Oncology. Marina Y. Konopleva received grants from the National Institutes of Health, the National Cancer Institute, AbbVie, Genentech, Stemline Therapeutics, Forty‐Seven, Eli Lilly, Cellectis, Calithera, Ablynx, and Astra Zeneca; consulting/honorarium from AbbVie, Genentech, F. Hoffman La‐Roche, Stemline Therapeutics, Amgen, Forty‐Seven, and Kisoji; clinical trial support from Ascentage; and has stock in and receives royalties from Reata Pharmaceutical.
Publisher Copyright:
© 2021 American Cancer Society
PY - 2021/11/15
Y1 - 2021/11/15
N2 - Background: Relapsed/refractory (R/R) acute myeloid leukemia (AML) has poor outcomes. Although lower-intensity venetoclax-containing regimens are standard for older/unfit patients with newly diagnosed AML, it is unknown how such regimens compare with intensive chemotherapy (IC) for R/R AML. Methods: Outcomes of R/R AML treated with 10-day decitabine and venetoclax (DEC10-VEN) were compared with IC-based regimens including idarubicin with cytarabine, with or without cladribine, clofarabine, or fludarabine, with or without additional agents. Propensity scores derived from patient baseline characteristics were used to match DEC10-VEN and IC patients to minimize bias. Results: Sixty-five patients in the DEC10-VEN cohort were matched to 130 IC recipients. The median ages for the DEC10-VEN and IC groups were 64 and 58 years, respectively, and baseline characteristics were balanced between the 2 cohorts. DEC10-VEN conferred significantly higher responses compared with IC including higher overall response rate (60% vs 36%; odds ratio [OR], 3.28; P <.001), complete remission with incomplete hematologic recovery (CRi, 19% vs 6%; OR, 3.56; P =.012), minimal residual disease negativity by flow cytometry (28% vs 13%; OR, 2.48; P =.017), and lower rates of refractory disease. DEC10-VEN led to significantly longer median event-free survival compared with IC (5.7 vs 1.5 months; hazard ratio [HR], 0.46; 95% CI, 0.30-0.70; P <.001), as well as median overall survival (OS; 6.8 vs 4.7 months; HR, 0.56; 95% CI, 0.37-0.86; P =.008). DEC10-VEN was independently associated with improved OS compared with IC in multivariate analysis. Exploratory analysis for OS in 27 subgroups showed that DEC10-VEN was comparable with IC as salvage therapy for R/R AML. Conclusion: DEC10-VEN represents an appropriate salvage therapy and may offer better responses and survival compared with IC in adults with R/R AML.
AB - Background: Relapsed/refractory (R/R) acute myeloid leukemia (AML) has poor outcomes. Although lower-intensity venetoclax-containing regimens are standard for older/unfit patients with newly diagnosed AML, it is unknown how such regimens compare with intensive chemotherapy (IC) for R/R AML. Methods: Outcomes of R/R AML treated with 10-day decitabine and venetoclax (DEC10-VEN) were compared with IC-based regimens including idarubicin with cytarabine, with or without cladribine, clofarabine, or fludarabine, with or without additional agents. Propensity scores derived from patient baseline characteristics were used to match DEC10-VEN and IC patients to minimize bias. Results: Sixty-five patients in the DEC10-VEN cohort were matched to 130 IC recipients. The median ages for the DEC10-VEN and IC groups were 64 and 58 years, respectively, and baseline characteristics were balanced between the 2 cohorts. DEC10-VEN conferred significantly higher responses compared with IC including higher overall response rate (60% vs 36%; odds ratio [OR], 3.28; P <.001), complete remission with incomplete hematologic recovery (CRi, 19% vs 6%; OR, 3.56; P =.012), minimal residual disease negativity by flow cytometry (28% vs 13%; OR, 2.48; P =.017), and lower rates of refractory disease. DEC10-VEN led to significantly longer median event-free survival compared with IC (5.7 vs 1.5 months; hazard ratio [HR], 0.46; 95% CI, 0.30-0.70; P <.001), as well as median overall survival (OS; 6.8 vs 4.7 months; HR, 0.56; 95% CI, 0.37-0.86; P =.008). DEC10-VEN was independently associated with improved OS compared with IC in multivariate analysis. Exploratory analysis for OS in 27 subgroups showed that DEC10-VEN was comparable with IC as salvage therapy for R/R AML. Conclusion: DEC10-VEN represents an appropriate salvage therapy and may offer better responses and survival compared with IC in adults with R/R AML.
KW - acute myeloid leukemia (AML)
KW - decitabine
KW - intensive chemotherapy
KW - refractory
KW - relapsed
KW - venetoclax
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U2 - 10.1002/cncr.33814
DO - 10.1002/cncr.33814
M3 - Article
C2 - 34343352
AN - SCOPUS:85111675964
SN - 0008-543X
VL - 127
SP - 4213
EP - 4220
JO - Cancer
JF - Cancer
IS - 22
ER -