Outcome of High-Risk Myelodysplastic Syndrome After Azacitidine Treatment Failure
Open accessAbstract
Purpose: Azacitidine (AZA) is the current standard of care for high-risk (ie, International Prognostic Scoring System high or intermediate 2) myelodysplastic syndrome (MDS), but most patients will experience primary or secondary treatment failure. The outcome of these patients has not yet been described. Patients and Methods: Overall, 435 patients with high-risk MDS and former refractory anemia with excess blasts in transformation (RAEB-T) were evaluated for outcome after AZA failure. The cohort of patients included four data sets (ie, AZA001, J9950, and J0443 trials and the French compassionate use program). Results: The median follow-up after AZA failure was 15 months. The median overall survival was 5.6 months, and the 2-year survival probability was 15%. Increasing age, male sex, high-risk cytogenetics, higher bone marrow blast count, and the absence of prior hematologic response to AZA were associated with significantly worse survival in multivariate analysis. Data on treatment administered after AZA failure were available for 270 patients. Allogeneic stem-cell transplantation and investigational agents were associated with a better outcome when compared with conventional clinical care. Conclusion: Outcome after AZA failure is poor. Our results should serve as a basis for designing second-line clinical trials in this population.
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Combination therapies in MDS including HDAC inhibitors, lenalidomide, pevonedistat, and anthracyclines have not improved results.
“Combination therapies in this setting have included HDAC inhibitors, 33 , 34 , 35 lenalidomide, 36 pevonedistat, 37 and anthracyclines 38 all without improved results.”
From Long‐term follow‐up and combined Phase 2 results of eprenetapopt and azacitidine in patients with <i>TP53</i> mutant MDS/AML (2025) · cites this paper as [34]
In Results > Patient Characteristics (page not provided), the paper lists anthracyclines among agents combined with azacitidine and reports no overall-survival difference between cohorts. It does not establish that the anthracycline combination itself failed to improve outcomes; the listed combinations were given during azacitidine treatment, not specifically after its failure. The other agents in the citing sentence have separate citations and are not attributed to this paper. (LLM, conf=0.85)
Experimental — accuracy not yet measuredAZA alone continues to represent standard of care in MDS because all recent studies have failed to improve median OS compared to monotherapy.
“AZA alone continues to represent the standard of care in MDS because all recent studies have failed to improve the median OS compared to monotherapy.”
From Long‐term follow‐up and combined Phase 2 results of eprenetapopt and azacitidine in patients with <i>TP53</i> mutant MDS/AML (2025) · cites this paper as [34]
The Introduction reports improved survival with AZA versus conventional care, and the Results (Patient Characteristics; OS After AZA Failure) report no OS difference between cohorts with different use of combination therapy and no effect of adding other drugs to the initial AZA schedule. But this study measures survival after AZA failure in high-risk MDS; it does not establish that all recent studies failed to improve median OS over AZA monotherapy or that AZA alone remains standard of care across MDS. Page numbers are unavailable in our copy. (LLM, conf=0.82)
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- Authors
- Prébet, T., Gore, S. D., Esterni, B., Gardin, C., Itzykson, R., Thepot, S., Dreyfus, F., Rauzy, O. B., Recher, C., Adès, L., Quesnel, B., Beach, C. L., Fenaux, P., & Vey, N.
- Affiliations
- Johns Hopkins University (US)
- Thomas Prébet, Steven D. Gore, Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD; Thomas Prébet, Benjamin Esterni, Norbert Vey, Institut Paoli Calmettes, Marseille, France; Thomas Prébet, Claude Gardin, Raphael Itzykson, Sylvain Thepot, François Dreyfus, Odile Beyne Rauzy, Christian Recher, Lionel Adès, Bruno Quesnel, Pierre Fenaux, Norbert Vey, Groupe Francophone des Myelodysplasies, Bobigny, France; C.L. Beach, Celgene, Summit, NJ.
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2011-08-20
- Volume
- 29
- Issue
- 24
- Pages
- 3322-3327
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC4859209
- OpenAlex
- W2131593570
- Cited by
- 475
- References
- 32
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 22 · 2023: 37 · 2022: 29 · 2021: 44 · 2020: 44 · 2019: 29 · 2018: 22 · 2017: 42 · 2016: 44 · 2015: 31 · 2014: 36 · 2013: 32 · 2012: 27
- FWCI
- 21.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA100904, K24CA111717, R01CA125635, R21CA110507, P30CA006973)
- National Center for Research Resources (M01RR000052)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- myelodysplastic syndrome, azacitidine, treatment failure, refractory anemia with excess blasts in transformation, overall survival, prognostic factors, allogeneic stem cell transplantation, second-line therapy, cytogenetics, bone marrow blast count, compassionate use
- MeSH terms
- Aged, Antimetabolites, Antineoplastic, Azacitidine, Female, Follow-Up Studies, Humans, Male, Middle Aged, Myelodysplastic Syndromes, Prognosis, Cohort Studies, Treatment Failure
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