Outcomes of TP53‐mutant acute myeloid leukemia with decitabine and venetoclax
Open accessAbstract
Background: TP53 mutation (TP53mut) confers an adverse prognosis in acute myeloid leukemia (AML). Venetoclax with hypomethylating agents is a current standard for older patients; however, recent reports suggest that TP53mut confers resistance to venetoclax. The authors investigated the outcomes of patients with TP53mut AML who were treated with a 10‐day decitabine and venetoclax (DEC10‐VEN) (ClinicalTrials.gov identifier NCT03404193). Methods: Patients with newly diagnosed AML received decitabine 20 mg/m 2 for 10 days every 4 to 6 weeks for induction, followed by decitabine for 5 days after response. The venetoclax dose was 400 mg daily. TP53mut was identified in bone marrow samples using next‐generation sequencing, with sensitivity of 5%. Outcomes were analyzed according to European LeukemiaNet 2017 guidelines. Results: Among 118 patients (median age, 72 years; age range, 49‐89 years), 63 (53%) had secondary AML, 39 (33%) had AML with complex karyotype, and 35 (30%) had TP53mut AML. The median TP53 variant allele frequency was 32% (interquartile range, 16%‐65%), 8 patients (23%) had only a single TP53 mutation, 15 (43%) had multiple mutations, and 12 (34%) had mutation and deletion. Outcomes were significantly worse in patients who had TP53mut AML compared with those who had wild‐type TP53 AML, with an overall response rate of 66% vs 89% (P = .002), a complete response/complete response with incomplete hematologic recovery rate of 57% vs 77% (P = .029), and a 60‐day mortality of 26% vs 4% (P < .001), respectively. Patients with TP53mut versus wild‐type TP53 had shorter overall survival at 5.2 versus 19.4 months, respectively (hazard ratio, 4.67; 95% CI, 2.44‐8.93; P < .0001), and shorter relapse‐free survival at 3.4 versus 18.9 months (hazard ratio, 4.80; 95% CI, 1.97‐11.69; P < .0001), respectively. Outcomes with DEC10‐VEN in patients with TP53mut AML were comparable to historical results with 10‐day decitabine alone. Conclusions: Patients with TP53mut AML have lower response rates and shorter survival with DEC10‐VEN.
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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 [32]
The Results report a 57% CR/CRi rate and 5.2-month median overall survival in TP53-mutant AML, and find no significant survival difference from decitabine alone. But this study tested decitabine plus venetoclax, not AZA plus venetoclax; the retrieved passages also do not establish a ~20% true CR rate or that the no-improvement finding was observed across multiple studies. The Discussion cautions against comparisons with azacitidine-based regimens. (LLM, conf=0.87)
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“32 Additionally, we observed an increase in CR rate at 41% with a median OS of 11.8 months.”
InfluentialSelf-citation
- Authors
- Kim, K., Maiti, A., Loghavi, S., Pourebrahim, R., Kadia, T. M., Rausch, C. R., Furudate, K., Daver, N. G., Alvarado, Y., Ohanian, M., Sasaki, K., Short, N. J., Takahashi, K., Yilmaz, M., Tang, G., Ravandi, F., Kantarjian, H. M., DiNardo, C. D., & Konopleva, M. Y.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Konopleva, Marina Y.
- ORCID
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2021-07-13
- Volume
- 127
- Issue
- 20
- Pages
- 3772-3781
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- PMC
- PMC10462434
- OpenAlex
- W3177711368
- Cited by
- 161
- References
- 29
- Citations by year
- 2026: 24 · 2025: 26 · 2024: 26 · 2023: 47 · 2022: 32 · 2021: 6
- FWCI
- 18.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01CA235622)
- American Society of Clinical Oncology (Young Investigator Award)
- National Cancer Institute (MD Anderson Cancer Center Support Grant CA016672)
- 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 › Chronic Myeloid Leukemia Treatments
- Keywords
- TP53 mutation, acute myeloid leukemia, decitabine, venetoclax, hypomethylating agents, venetoclax resistance, overall survival, complete response, secondary acute myeloid leukemia, complex karyotype, variant allele frequency, elderly patients, induction therapy, prognostic factors
- MeSH terms
- Decitabine, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Humans, Middle Aged, Sulfonamides, Leukemia, Myeloid, Acute, Tumor Suppressor Protein p53, Bridged Bicyclo Compounds, Heterocyclic
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