Talha Badar, Associate Professor at Mayo Clinic Comprehensive Cancer Center, shared on X:
“For a decade, decitabine has been assumed superior to azacitidine in TP53-mutant AML based on deeper molecular clearance. We tested that assumption in 652 patients across 15 centers.
Does AZA vs DEC choice matter in TP53-mutant AML?
We tested the myth in 652 pts from the COMMAND registry (15 centers/Fig A). Fig B: duration of response was heterogeneous in both arms, no consistent DEC advantage in durability.
Headline: EFS (P=0.689) and OS (P=0.836) were NOT different across DEC/VEN, AZA/VEN, DEC, or AZA in 321 pts with TP53-mutant AML. CR/CRi favored DEC (54% vs 39%) but that response edge did not translate into a survival benefit. Retrospective registry data.
What DID matter: alloHCT. 90-day landmark OS 36.8mo (AZA/HCT) and 23.3mo (DEC/HCT) vs 9.4 and 10.4mo without transplant (P<0.001). Multi-hit TP53 independently predicted worse EFS/OS (HR approximately 2), not HMA backbone.
Propensity-matched cohort (n=216) confirmed no difference: EFS P=0.920, OS P=0.925. Bottom line: choose the HMA on tolerability and logistics, not an expected survival gain, and prioritize early transplant referral in TP53-mutant AML. Badar et al, Leukemia 2026.
Title: Choice of hypomethylating agent for newly diagnosed TP53-mutant acute myeloid Leukemia: a COMMAND registry study
Authors: Talha Badar, James Foran, Omer Jamy, Chenyu Lin, Anand Patel, Yu-Hung Wang, Mahesh Kumar, Rory M. Shallis, Kendall Diebold, Alexander Colton, 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.
Read the full article.
You can find this interesting: TP53-Mutated MDS: Can New Therapies Change the Prognosis?
