Comparing venetoclax in combination with hypomethylating agents to hypomethylating agent-based therapies for treatment naive TP53-mutated acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND)
Open accessAbstract
TP53 is a tumor suppressor gene located on the short arm of chromosome 17(p13), known to be involved in multiple cellular processes and regulate cell proliferation by responding to various stress [ 1 , 2 ]. TP53 is a frequently mutated (m) gene found across diverse types of cancers, strongly linked to large structural and complex chromosomal abnormalities [ 3 , 4 ]. It is reported in 5–10% of patients diagnosed with acute myeloid leukemia (AML), more prevalent among the elderly and those with therapy-related AML and/or complex cytogenetics (CG). AML with TP53 mutations is associated with poor prognosis and inferior responses to traditional therapies [ 3 , 4 ].
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AZA + VEN leads to CRc rate ~60%, true CR ~20%, with no improvement in median OS ~6 months in mTP53 AML across multiple studies.
“AZA + VEN has emerged as the standard of care for all subtypes of AML in older and unfit patients, but the combination remains controversial in mTP53 AML because even though the combination leads to a CRc rate of approximately 60%, the true CR rate was ~20% with no improvement of the median OS of approximately 6 months observed across multiple studies”
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 [42]
The paper’s results and discussion (page not given in our copy) report no overall-survival improvement with HMA + VEN in TP53-mutated AML, and summarize median OS of 6.0–11.0 months across prior reports. But they do not report a composite remission rate of approximately 60%; this study reports a CR rate of 35% with HMA + VEN, while its literature summary gives CR rates of 20–40%, rather than a consistent true CR rate of approximately 20%. Its own HMA + VEN median OS was 7.3 months, not approximately 6 months. (LLM, conf=0.88)
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Cites
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Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia
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Self-citationBadar, T., Atallah, E. L., Shallis, R. M., Saliba, A. N., Patel, A. A., Bewersdorf, J. P., Grenet, J. E., Stahl, M. F., DuVall, A. S., Burkart, M., et al. (2023) · Leukemia · doi:10.1038/s41375-023-01847-7 · Cited by 65 · see citing works
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Sallman, D. A., Komrokji, R. S., Dezern, A. E., Sebert, M., Garcia‐Manero, G., Rahmé, R., Winer, E. S., Lehmann‐Che, J., Roboz, G. J., Madelaine, I., et al. (2025) · HemaSphere · doi:10.1002/hem3.70164 · Cited by 20 · see citing works
- Authors
- Badar, T., Nanaa, A., Atallah, E., Shallis, R. M., Guilherme, S. D. C. C., Goldberg, A. D., Saliba, A. N., Patel, A., Bewersdorf, J. P., DuVall, A. S., Bradshaw, D., Abaza, Y., Murthy, G. S. G., Palmisiano, N., Zeidan, A. M., Kota, V., & Litzow, M. R.
- Affiliations
- Mayo Clinic in Florida (US)
- Mayo Clinic (US)
- Medical College of Wisconsin (US)
- Yale University (US)
- Mount Sinai Health System (US)
- Memorial Sloan Kettering Cancer Center (US)
- University of Chicago (US)
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University (US)
- Thomas Jefferson University Hospital (US)
- Corresponding author
- Badar, Talha
- ORCID
- Venue
- Blood Cancer Journal
- Published
- 2024-02-20
- Volume
- 14
- Issue
- 1
- Pages
- 32-32
- ISSN
- 2044-5385 (ISSN-L)
- PMC
- PMC10879201
- OpenAlex
- W4391981561
- Cited by
- 33
- References
- 15
- Citations by year
- 2026: 2 · 2025: 18 · 2024: 12
- FWCI
- 9.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Blood Cancer Journal (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- American Society of Hematology
- Yale University
- Memorial Sloan-Kettering Cancer Center (CA008748, P30 CA008748)
- Northwestern University
- Mount Sinai Health System
- National Institutes of Health (CA008748, CA23766, CA016359, UL1TR001863)
- Robert H. Lurie Comprehensive Cancer Center
- National Cancer Institute (P01CA023766, P01CA23766, CA008748, CA23 766, CA-016359, R01CA237660, P30CA008748, 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 › Genetics › Chronic Lymphocytic Leukemia Research
- Keywords
- venetoclax, hypomethylating agents, TP53 mutation, acute myeloid leukemia, treatment-naive patients, combination therapy, complex cytogenetics, therapy-related AML, prognosis
- MeSH terms
- Antineoplastic Combined Chemotherapy Protocols, Humans, Sulfonamides, Leukemia, Myeloid, Acute, Tumor Suppressor Protein p53, Bridged Bicyclo Compounds, Heterocyclic
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