Clinical outcomes of older patients with AML receiving hypomethylating agents: a large population-based study in the United States
Open accessAbstract
The hypomethylating agents (HMAs) azacitidine and decitabine have been the de facto standard of care for patients with acute myeloid leukemia (AML) who are unfit for intensive therapy. Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified 2263 older adults (age ≥66 years) diagnosed with AML during 2005-2015 who received a first-line HMA; 1154 (51%) received azacitidine, and 1109 (49%) received decitabine. Median survival from diagnosis was 7.1 and 8.2 months (P < .01) for azacitidine- and decitabine-treated patients, respectively. Mortality risk was higher with azacitidine vs decitabine (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.01-1.21; P = .02). The findings were similar when evaluating only patients completing ≥4 cycles (42% of patients treated with either azacitidine or decitabine). These findings lost significance when evaluating those completing a standard 7-day schedule of azacitidine (34%) vs 5-day schedule for decitabine (66%) (HR, 0.95; 95% CI, 0.83-1.08; P = .43). Red blood cell (RBC) transfusion independence (TI) was achieved in one-third of patients with no difference between the 2 HMAs. In conclusion, the majority of older AML patients did not receive the minimum of 4 cycles of HMA often needed to elicit clinical benefit. We observed no clinically meaningful differences between azacitidine- and decitabine-treated patients in their achievement of RBC TI or survival.
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Increased HMA duration, such as 10-day decitabine, initially suggested improved outcomes in a limited number of patients with TP53-mutant myeloid malignancies, but there was no improvement in CR or OS in a prospective randomized study comparing 10-day versus 5-day decitabine in AML.
“Increased HMA duration, such as 10-day decitabine, initially suggested improved outcomes in a limited number of patients with TP53-mutant myeloid malignancies (patients with MDS; n = 9),18 but there was no improvement in CR or OS in a prospective randomized study comparing 10-day versus 5-day decitabine in AML, and this treatment schedule has not been widely adopted.19,20”
From Eprenetapopt (APR-246) and Azacitidine in <i>TP53</i> -Mutant Myelodysplastic Syndromes (2021) · cites this paper as [20]
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Eprenetapopt (APR-246) and Azacitidine in <i>TP53</i> -Mutant Myelodysplastic Syndromes
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“Alanine aminotransferase increased 11 (20) 1 (2)”
Influential
- Authors
- 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., Davidoff, A. J., & Ma, X.
- Affiliations
- Department of Internal Medicine,
- Cancer Outcomes, Public Policy, and Effectiveness Research Center,
- Yale University (US)
- ORCID
- Venue
- Blood Advances
- Publisher
- American Society of Hematology
- Published
- 2020-05-20
- Volume
- 4
- Issue
- 10
- Pages
- 2192-2201
- ISSN
- 2473-9529 (ISSN-L)
- 2473-9537
- PMC
- PMC7252544
- OpenAlex
- W3028372384
- Cited by
- 93
- References
- 39
- Citations by year
- 2026: 9 · 2025: 5 · 2024: 10 · 2023: 17 · 2022: 21 · 2021: 23 · 2020: 7 · 2019: 1
- FWCI
- 10.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Blood Advances (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Celgene
- National Institutes of Health (n01pc35139-25-0-11, n01pc35136-24-0-2, UL1TR001863)
- National Cancer Institute (N01 PC035139, N01 PC035136, N02 PC015105, P30CA016359)
- National Center for Advancing Translational Sciences
- 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
- acute myeloid leukemia, hypomethylating agents, azacitidine, decitabine, older adults, first-line therapy, survival, mortality, treatment duration, red blood cell transfusion independence
- MeSH terms
- Decitabine, Aged, Medicare, Humans, Retrospective Studies, United States, Leukemia, Myeloid, Acute, Treatment Outcome
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