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Publications

Journal Article Ahead of print 1 citation

PubMed: 42675141 DOI: 10.1038/s41375-026-03119-6

Choice of hypomethylating agent for newly diagnosed TP53-mutant acute myeloid Leukemia: a COMMAND registry study.

Leukemia

Authors: Talha Badar, James Foran, Omer Jamy, Chenyu Lin, Anand Patel, Yu-Hung Wang, Mahesh Kumar, Rory M Shallis, Kendall Diebold, Alexander Coltoff, Aaron D Goldberg, Jan P Bewersdorf, Kenneth M Zabel, Charles Foucar, Yasmin Abaza, Guru S Murthy, Neil Palmisiano, Adam S DuVall, Vamsi Kota, Shyam A Patel, Amer M Zeidan, Hemant Murthy, Mohamed Kharfan-Dabaja, Ehab Atallah, Mark R Litzow

Affiliations

  • Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, FL, USA.
  • Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, FL, USA.
  • Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, AL, USA.
  • Division of Hematologic Malignancies and Cellular Therapy, Duke University School of Medicine, Durham, NC, USA.
  • Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.
  • Division of Hematology and Oncology, Institution: National Taiwan University Cancer Center, Taipei, Taiwan.
  • Section of Medical Oncology and Hematology, Department of Internal Medicine, Yale School of Medicine and Yale Comprehensive Cancer Center, New Haven, CT, USA.
  • Division of Hematology and Oncology, Medical University of South Carolina, Charleston, SC, USA.
  • Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
  • Division of Hematology and Oncology, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.
  • Robert H. Lurie Comprehensive Cancer Center, Northwestern Hospital, Chicago, IL, USA.
  • Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Division of Hematology and Oncology, Rutgers Cancer Institute, New Brunswick, NJ, USA.
  • Division of Hematology and Oncology, Augusta University, Augusta, GA, USA.
  • Department of Medicine-Division of Hematology/Oncology, UMass Memorial Medical Center, UMass Chan Medical School, Worcester, MA, USA.
  • Division of Hematology, Mayo Clinic, Rochester, MN, USA.

Abstract

Although azacitidine (AZA) and decitabine (DEC) demonstrate comparable efficacy in AML, prior data suggest that DEC may induce deeper TP53 mutation clearance and higher response rates; however, direct comparisons in TP53-mutant (TP53-MT) AML are lacking. We conducted a large multicenter retrospective analysis to compare outcomes between DEC- and AZA-based induction, including combinations with venetoclax (VEN). Of 652 patients with newly diagnosed TP53-MT AML, 321 received HMA-based induction (DEC, n = 183; AZA, n = 138). Baseline clinical and genomic characteristics were comparable between the DEC and AZA groups. TP53 mutation subtype were not associated with outcomes, whereas multi-hit TP53 status was independently associated with inferior EFS and OS. In the propensity score-matched cohort, no significant differences in event-free survival (EFS; P = 0.920) or overall survival (OS; P = 0.927) were observed. Median EFS was 5.1, 3.4, 5.9, and 5.6 months, with 12-month estimates of 24%, 17%, 18%, and 16%, while median OS was 5.7, 7.1, 9.2, and 7.1 months, with corresponding 12-month OS rates of 31%, 23%, 29%, and 32% for DEC + VEN, AZA + VEN, DEC, and AZA, respectively. No significant pairwise differences were observed between regimens. These findings from a large multicenter cohort suggest that AZA- and DEC-based induction yield comparable survival outcomes in TP53-MT AML.

MeSH

Registries, Multiple Chronic Conditions, Leukemia, Leukemia, Myeloid, Acute, Leukemia, Myeloid, Mutation