Azacitidine Prolongs Overall Survival Compared With Conventional Care Regimens in Elderly Patients With Low Bone Marrow Blast Count Acute Myeloid Leukemia
Open accessAbstract
Purpose: In a phase III randomized trial, azacitidine significantly prolonged overall survival (OS) compared with conventional care regimens (CCRs) in patients with intermediate-2– and high-risk myelodysplastic syndromes. Approximately one third of these patients were classified as having acute myeloid leukemia (AML) under current WHO criteria. This analysis compared the effects of azacitidine versus CCR on OS in this subgroup. Patients and Methods: Patients were randomly assigned to receive subcutaneous azacitidine 75 mg/m 2 /d or CCR (best supportive care [BSC] only, low-dose cytarabine (LDAC), or intensive chemotherapy [IC]). Results: Of the 113 elderly patients (median age, 70 years) randomly assigned to receive azacitidine (n = 55) or CCR (n = 58; 47% BSC, 34% LDAC, 19% IC), 86% were considered unfit for IC. At a median follow-up of 20.1 months, median OS for azacitidine-treated patients was 24.5 months compared with 16.0 months for CCR-treated patients (hazard ratio = 0.47; 95% CI, 0.28 to 0.79; P = .005), and 2-year OS rates were 50% and 16%, respectively (P = .001). Two-year OS rates were higher with azacitidine versus CCR in patients considered unfit for IC (P = .0003). Azacitidine was associated with fewer total days in hospital (P < .0001) than CCR. Conclusion: In older adult patients with low marrow blast count (20% to 30%) WHO-defined AML, azacitidine significantly prolongs OS and significantly improves several patient morbidity measures compared with CCR.
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The prolonged time to initial response, typically around 3 months from treatment onset, is consistent with the primary effects of low dose treatment being mediated via DNA demethylation and epigenetic reprogramming as opposed to direct cytotoxicity.
“The prolonged time to initial response, which typically occurs around 3 months from treatment onset 125 , is consistent with the primary effects of low dose treatment being mediated via DNA demethylation and epigenetic reprogramming as opposed to direct cytotoxicity 126-128 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [128]
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Cites
International scoring system for evaluating prognosis in myelodysplastic syndromes
Greenberg, P., Cox, C., LeBeau, M. M., Fenaux, P., Morel, P., Sanz, G., Sanz, M., Vallespi, T., Hamblin, T., Oscier, D., et al. (1997) · Blood · doi:10.1182/blood.v89.6.2079 · Cited by 4,427 · see citing works
Self-citationProposals for the classification of the myelodysplastic syndromes
Bennett, J. M., Catovsky, D., Daniel, M., Flandrin, G., Galton, D. A. G., Gralnick, H. R., & Sultan, C. (1982) · British Journal of Haematology · doi:10.1111/j.1365-2141.1982.tb08475.x · Cited by 3,619 · see citing works
Harris, N. L., Jaffe, E. S., Diebold, J., Flandrin, G., Müller‐Hermelink, H. K., Vardiman, J. W., Lister, T. A., & Bloomfield, C. D. (1999) · Journal of Clinical Oncology · doi:10.1200/jco.1999.17.12.3835 · Cited by 3,261 · see citing works
Cheson, B. D., Bennett, J. M., Kopecky, K. J., Büchner, T., Willman, C. L., Estey, E. H., Schiffer, C. A., Döhner, H., Tallman, M. S., Lister, T. A., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.04.036 · Cited by 2,686 · see citing works
Fenaux, P., Mufti, G. J., Hellstrom-Lindberg, E., Santini, V., Finelli, C., Giagounidis, A., Schoch, R., Gattermann, N., Sanz, G., List, A., et al. (2009) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70003-8 · Cited by 2,663 · see citing works
Self-citationThe World Health Organization (WHO) classification of the myeloid neoplasms
Vardiman, J. W., Harris, N. L., & Brunning, R. D. (2002) · Blood · doi:10.1182/blood-2002-04-1199 · Cited by 2,191 · see citing works
Creutzig, U., & Kaspers, G. J. L. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.99.116 · Cited by 2,137 · see citing works
Age and acute myeloid leukemia
Appelbaum, F. R., Gundacker, H. M., Head, D. R., Slovak, M. L., Willman, C. L., Godwin, J. E., Anderson, J. E., & Petersdorf, S. H. (2006) · Blood · doi:10.1182/blood-2005-09-3724 · Cited by 1,352 · see citing works
Löwenberg, B., Downing, J. R., & Burnett, A. K. (1999) · New England Journal of Medicine · doi:10.1056/nejm199909303411407 · Cited by 1,283 · see citing works
Burnett, A. K., Milligan, D., Prentice, A. G., Goldstone, A. H., McMullin, M. F., Hills, R. K., & Wheatley, K. (2007) · Cancer · doi:10.1002/cncr.22496 · Cited by 619 · see citing works
Kantarjian, H. M., O'Brien, S. M., Cortes, J. E., Giles, F. J., Faderl, S. H., Jabbour, E. J., Garcia‐Manero, G., Wierda, W. G., Pierce, S. A., Shan, J., et al. (2006) · Cancer · doi:10.1002/cncr.21723 · Cited by 608 · see citing works
Silverman, L. R., McKenzie, D. R., Peterson, B. L., Holland, J. F., Backstrom, J. T., Beach, C. L., & Larson, R. A. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.05.4346 · Cited by 550 · see citing works
Self-citationGuidelines for the diagnosis and therapy of adult myelodysplastic syndromes
Bowen, D., Culligan, D. J., Jowitt, S. N., Kelsey, S. M., Mufti, G. J., Oscier, D. G., Parker, J., & of the UK MDS Guidelines Group (2003) · British Journal of Haematology · doi:10.1046/j.1365-2141.2003.03907.x · Cited by 300 · see citing works
Self-citationGerming, U., Gattermann, N., Strupp, C., Aivado, M. A., & Aul, C. (2000) · Leukemia Research · doi:10.1016/s0145-2126(00)00088-6 · Cited by 296 · see citing works
Self-citationRowe, J. M., Neuberg, D. S., Friedenberg, W. R., Bennett, J. M., Paietta, E. M., Makary, A. Z., Liesveld, J. L., Abboud, C. N., Dewald, G. W., Hayes, F. A., et al. (2003) · Blood · doi:10.1182/blood-2003-05-1686 · Cited by 277 · see citing works
The Outcomes and Costs of Acute Myeloid Leukemia Among the Elderly
Menzin, J., Lang, K., Earle, C. C., Kerney, D. L., & Mallick, R. (2002) · Archives of Internal Medicine · doi:10.1001/archinte.162.14.1597 · Cited by 276 · see citing works
Tilly, H., Castaigné, S., Bordessoule, D., Casassus, P., Prisé, P. Y. L., Tertian, G., Desablens, B., Henry-Amar, M., & Degos, L. (1990) · Journal of Clinical Oncology · doi:10.1200/jco.1990.8.2.272 · Cited by 259 · see citing works
Estey, E. H., Thall, P. F., Beran, M., Kantarjian, H. M., Pierce, S. A., & Keating, M. J. (1997) · Blood · doi:10.1182/blood.v90.8.2969 · Cited by 229 · see citing works
Löwenberg, B., Suciu, S., Archimbaud, E., Ossenkoppele, G. J., Verhoef, G. E. G., Vellenga, E., Wijermans, P., Berneman, Z. N., Dekker, A. W., Stryckmans, P. A., et al. (1997) · PubMed · doi:10.1182/blood.v90.8.2952 · Cited by 205 · see citing works
Faderl, S. H., Ravandi, F., Huang, X., Garcia‐Manero, G., Ferrajoli, A., Estrov, Z. E., Borthakur, G. M., Verstovšek, S., Thomas, D. A., Kwari, M. I., et al. (2008) · Blood · doi:10.1182/blood-2007-11-124602 · Cited by 199 · see citing works
Anderson, J. E., Kopecky, K. J., Willman, C. L., et al. (2002) · Blood · doi:10.1182/blood-2001-12-0354 · Cited by 192 · see citing works
Alessandrino, E. P., Amadori, S., Barosi, G., Cazzola, M., Grossi, A., Liberato, L. N., Locatelli, F., Marchetti, M., Morra, E., Rebulla, P., et al. (2002) · PubMed · Cited by 178 · see citing works
Gardin, C., Turlure, P., Fagot, T., Thomas, X., Terré, C., Contentin, N., Raffoux, E., de Botton, S., Pautas, C., Reman, O., et al. (2007) · Blood · doi:10.1182/blood-2007-02-069666 · Cited by 174 · see citing works
Self-citationHarousseau, J., Martinelli, G., Wiktor-Jędrzejczak, W., Brandwein, J. M., Bordessoule, D., Masszi, T., Ossenkoppele, G. J., Alexeeva, J. A., Beutel, G., Maertens, J. A., et al. (2009) · Blood · doi:10.1182/blood-2009-01-198093 · Cited by 149 · see citing works
Self-citationForman, S. J., Slovak, M. L., Arber, D. A., et al. (2003) · American Journal of Clinical Pathology · doi:10.1309/em7k-cqr4-glmh-rcx4 · Cited by 147 · see citing works
Estey, E. H., Thall, P. F., Giles, F. J., Wang, X., Cortes, J. E., Beran, M., Pierce, S. A., Thomas, D. A., & Kantarjian, H. M. (2002) · Blood · doi:10.1182/blood.v99.12.4343 · Cited by 138 · see citing works
Deschler-Baier, B., de Witte, T., Mertelsmann, R. H., & Lübbert, M. (2006) · PubMed · Cited by 138 · see citing works
Prognostic Impact of Acute Myeloid Leukemia Classification
Arber, D. A., Stein, A. S., Carter, N. H., et al. (2003) · American Journal of Clinical Pathology · doi:10.1309/em7kcqr4glmhrcx4 · Cited by 119 · see citing works
Knipp, S., Hildebrand, B., Kündgen, A., Giagounidis, A. A. N., Kobbe, G., Haas, R. R., Aul, C., Gattermann, N., & Germing, U. (2007) · Cancer · doi:10.1002/cncr.22779 · Cited by 112 · see citing works
Self-citationFenaux, P., Raza, A., Mufti, G. J., Aul, C., Germing, U., Kantarjian, H. M., Cripe, L. D., Kerstens, R., Porre, P. D., & Kurzrock, R. (2007) · Blood · doi:10.1182/blood-2006-07-035725 · Cited by 104 · see citing works
Self-citationGiles, F. J., Rizzieri, D. A., Karp, J. E., Vey, N., Ravandi, F., Faderl, S. H., Khan, K. D., Verhoef, G. E. G., Wijermans, P., Advani, A. S., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.07.0961 · Cited by 84 · see citing works
Self-citationHellström‐Lindberg, E., Robèrt, K., Gahrton, G., Lindberg, G., Forsblom, A., Kock, Y., & Öst, Å. (1992) · British Journal of Haematology · doi:10.1111/j.1365-2141.1992.tb02982.x · Cited by 76 · see citing works
Self-citationCheson, B. D., & Simon, R. M. (1987) · PubMed · Cited by 68 · see citing works
Classification of acute leukemias
Brunning, R. D. (2003) · Seminars in Diagnostic Pathology · doi:10.1016/s0740-2570(03)00031-5 · Cited by 60 · see citing works
Acute Myeloid Leukemia in the Elderly
Dombret, H., Raffoux, E., & Gardin, C. (2008) · Seminars in Oncology · doi:10.1053/j.seminoncol.2008.04.013 · Cited by 58 · see citing works
Self-citationTreatment of acute myeloid leukemia
Estey, E. H. (2008) · Haematologica · doi:10.3324/haematol.2008.001263 · Cited by 56 · see citing works
Bernstein, S. H., Brunetto, V. L., Davey, F. R., et al. (1996) · Journal of Clinical Oncology · doi:10.1200/jco.1996.14.9.2486 · Cited by 56 · see citing works
Strupp, C., Gattermann, N., Giagounidis, A. A. N., et al. (2003) · Leukemia Research · doi:10.1016/s0145-2126(02)00220-5 · Cited by 43 · see citing works
Self-citationAcute myeloid leukemia in the elderly: Conventional and novel treatment approaches
Craig, C. M., & Schiller, G. J. (2008) · Blood Reviews · doi:10.1016/j.blre.2008.03.002 · Cited by 40 · see citing works
Burnett, A. K., Baccarani, M., Johnson, P. R. E., et al. (2006) · Blood · doi:10.1182/blood.v108.11.425.425 · Cited by 34 · see citing works
Antibody-targeted chemotherapy for the treatment of relapsed acute myeloid leukemia.
Jp, W., & Hl, H. (2000) · PubMed · Cited by 22 · see citing works
Albitar, M. X., Beran, M., O'Brien, S. M., et al. (2000) · Blood · doi:10.1182/blood.v96.1.372.013k56c_372_374 · Cited by 21 · see citing works
Erba, H. P., Kantarjian, H. M., Claxton, D. F., et al. (2008) · Blood · doi:10.1182/blood.v112.11.558.558 · Cited by 17 · see citing works
Albitar, M. X., Beran, M., O'Brien, S. M., et al. (2000) · Blood · doi:10.1182/blood.v96.1.372 · Cited by 17 · see citing works
Menzin, J., Boulanger, L., Karsten, V., et al. (2006) · Blood · doi:10.1182/blood.v108.11.1973.1973 · Cited by 16 · see citing works
Detourmignies, L., Wattel, E., Laı̈, J. L., Bauters, F., & Fenaux, P. (1993) · Annals of Hematology · doi:10.1007/bf01738471 · Cited by 16 · see citing works
Self-citation(1998) · Blood · doi:10.1182/blood.v91.3.1100 · Cited by 9 · see citing works
Fukuhara, T., Miyake, T., Maekawa, I., et al. (2000) · PubMed · Cited by 7 · see citing works
Acute Leukemia in Patients Sixty Years of Age and Older
Leger, C. S., Leitch, H. A., Galbraith, P. F., Li, C. H., & Vickars, L. M. (2009) · American Journal of Clinical Oncology · doi:10.1097/coc.0b013e31818a6c93 · Cited by 4 · see citing works
Breccia, M., Latagliata, R., Carmosino, I., et al. (2007) · Acta Haematologica · doi:10.1159/000098957 · Cited by 3 · see citing works
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Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia
DiNardo, C. D., Jonas, B. A., Pullarkat, V., Thirman, M. J., Garcia, J. S., Wei, A. H., Konopleva, M., Döhner, H., Letai, A., Fenaux, P., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2012971 · Cited by 2,900 · see citing works
Self-citationDiNardo, C. D., Pratz, K., Pullarkat, V., Jonas, B. A., Arellano, M., Becker, P. S., Frankfurt, O., Konopleva, M., Wei, A. H., Kantarjian, H. M., et al. (2019) · Blood · doi:10.1182/blood-2018-08-868752 · Cited by 1,825 · see citing works
Dombret, H., Seymour, J. F., Butrym, A., Wierzbowska, A., Selleslag, D., Jang, J. H., Kumar, R., Cavenagh, J., Schuh, A. C., Candoni, A., et al. (2015) · Blood · doi:10.1182/blood-2015-01-621664 · Cited by 1,165 · see citing works
Self-citationThe roles of DNA, RNA and histone methylation in ageing and cancer
Michalak, E. M., Burr, M. L., Bannister, A. J., & Dawson, M. A. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0143-1 · Cited by 549 · see citing works
Vitamin C increases viral mimicry induced by 5-aza-2′-deoxycytidine
Liu, M., Ohtani, H., Zhou, W., Ørskov, A. D., Charlet, J., Zhang, Y. W., Shen, H., Baylin, S. B., Liang, G., Grønbæk, K., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1612262113 · Cited by 225 · see citing works
IDH1 and IDH2 mutations as novel therapeutic targets: current perspectives
de Botton, S., Mondesir, J., Willekens, C., & Touat, M. (2016) · Journal of Blood Medicine · doi:10.2147/jbm.s70716 · Cited by 220 · see citing works
Raffoux, E., Cras, A., Recher, C., Boëlle, P.-Y., de Labarthe, A., Turlure, P., Marolleau, J.-P., Reman, O., Gardin, C., Victor, M., et al. (2010) · Oncotarget · doi:10.18632/oncotarget.106 · Cited by 134 · see citing works
Self-citationCurrent status and new treatment approaches in TP53 mutated AML
Hunter, A. M., & Sallman, D. A. (2019) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2019.05.004 · Cited by 102 · see citing works
Fehniger, T. A., Uy, G. L., Trinkaus, K., Nelson, A. D., Demland, J., Abboud, C. N., Cashen, A. F., Stockerl-Goldstein, K. E., Westervelt, P., DiPersio, J. F., et al. (2011) · Blood · doi:10.1182/blood-2010-07-297143 · Cited by 107 · see citing works
Zeidan, A. M., Wang, R., Wang, X., Shallis, R. M., Podoltsev, N. A., Bewersdorf, J. P., Huntington, S. F., Neparidze, N., Giri, S., Gore, S. D., et al. (2020) · Blood Advances · doi:10.1182/bloodadvances.2020001779 · Cited by 93 · see citing works
Self-citationVasu, S., He, S., Cheney, C., Gopalakrishnan, B., Mani, R., Lozanski, G., Mo, X., Groh, V., Whitman, S. P., Konopitzky, R., et al. (2016) · Blood · doi:10.1182/blood-2015-11-680546 · Cited by 93 · see citing works
Craddock, C. F., Houlton, A. E., Quek, L. S., Ferguson, P., Gbandi, E., Roberts, C., Metzner, M., Garcia-Martin, N., Kennedy, A., Hamblin, A., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-1423 · Cited by 88 · see citing works
Digging deep into “dirty” drugs – modulation of the methylation machinery
Pleyer, L., & Greil, R. (2015) · Drug Metabolism Reviews · doi:10.3109/03602532.2014.995379 · Cited by 84 · see citing works
“Almost 35 years later, both drugs have shown significant clinical benefits with high overall response rates and improved overall survival in patients with myeloid malignancies (Fenaux et al., 2009, 2010; Kantarjian et al., 2012; Pleyer et al., 2013, 2014a, b).”
BackgroundSekeres, M. A., Gundacker, H., Lancet, J., Advani, A., Petersdorf, S., Liesveld, J., Mulford, D., Norwood, T., Willman, C. L., Appelbaum, F. R., et al. (2011) · Blood · doi:10.1182/blood-2011-02-337303 · Cited by 80 · see citing works
Self-citationFang, D. D., Tang, Q., Kong, Y., Rong, T., Wang, Q., Li, N., Fang, X., Gu, J., Xiong, D., Yin, Y., et al. (2021) · Cell Death Discovery · doi:10.1038/s41420-021-00465-5 · Cited by 58 · see citing works
- Authors
- Fenaux, P., Mufti, G. J., Hellström-Lindberg, E., Santini, V., Gattermann, N., Germing, U., Sanz, G., List, A. F., Gore, S., Seymour, J. F., Dombret, H., Backstrom, J., Zimmerman, L., McKenzie, D., Beach, C. L., & Silverman, L. R.
- Affiliations
- Karolinska University Hospital (SE)
- From the Avicenne, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris XIII, Bobigny; Hôpital Saint-Louis, AP-HP, Université Paris 7, Paris, France; King's College Hospital, London, United Kingdom; Karolinska University Hospital (Huddinge), Stockholm, Sweden; Azienda Ospedaliera Universitaria Careggi, Florence, Italy; Universitätsklinikum Düsseldorf, Düsseldorf, Germany; Hospital Universitario La Fe, Valencia, Spain; Peter MacCallum Cancer Centre and University of Melbourne, Melbourne,...
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2010-02-01
- Volume
- 28
- Issue
- 4
- Pages
- 562-569
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2157287007
- Cited by
- 961
- References
- 51
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 21 · 2023: 38 · 2022: 39 · 2021: 54 · 2020: 75 · 2019: 71 · 2018: 63 · 2017: 75 · 2016: 70 · 2015: 79 · 2014: 88 · 2013: 78 · 2012: 77
- FWCI
- 38.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Amgen
- GlaxoSmithKline
- Celgene
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- azacitidine, acute myeloid leukemia, elderly patients, overall survival, myelodysplastic syndrome, low-dose cytarabine, intensive chemotherapy, best supportive care, length of hospital stay
- MeSH terms
- Aged, Aged, 80 and over, Antimetabolites, Antineoplastic, Antineoplastic Combined Chemotherapy Protocols, Azacitidine, Blast Crisis, Bone Marrow Cells, Female, Follow-Up Studies, Humans, International Agencies, Leukocyte Count, Male, Middle Aged, Neoplasm Staging, Prognosis, Leukemia, Myeloid, Acute, Survival Rate, Treatment Outcome, Maximum Tolerated Dose
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