Clinical and genomic classification of secondary AML: Implications for prognosis and treatment

Secondary acute myeloid leukemia (sAML) represents a high-risk subset of AML with limited treatment options and historically poor outcomes, particularly in older adults. Although recent classifications incorporate both clinical and genomic criteria to define sAML, their prognostic relevance when receiving modern therapies such as venetoclax-based regimens remains unclear.

Researchers at The University of Texas MD Anderson Cancer Center conducted a large retrospective analysis of 1,380 patients with newly diagnosed AML. The study aimed to compare clinical and genomic forms of untreated sAML against de novo AML and explored treatment response by therapy type and molecular features. This work was recently published by Senapati et al. in the American Journal of Hematology.

Key learnings

Median OS and RFS were similar in patients with untreated CS-AML and GS-AML (11.6 vs 14.4 months and 11.9 vs 12.4 months, respectively). OS and RFS were substantially longer in patients with DN-AML (49.7 and 57.1 months, respectively).

Among GS-AML patients treated with LIT+VEN, median OS was 29.6 months in patients with MRM-only (n = 98), 8.8 months in those with MRC-only (n = 73), and 7.8 months in those with MRM+MRC (n = 30), reflecting outcome variability by genomic subtype.

In multivariable analysis of patients with GS-AML treated with LIT+VEN, TP53 mutations (HR, 2.49; 95% CI, 1.54–4.04; p < 0.01) and adverse vs non-adverse cytogenetics (HR, 1.82; 95% CI, 1.14–NE; p = 0.01) were independently associated with higher mortality. The ELN 2024 LIT risk stratification also had an independent prognostic impact.

Venetoclax-based therapy improves outcomes in GS-AML with MRM, with survival comparable to DN-AML. Outcomes remain poor in patients with MRC or adverse cytogenetics, supporting integration of genomic subtypes and ELN 2024 LIT risk stratification into treatment planning.