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

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.