Photo Credit: Md Babul Hosen
The following is a summary of “Clinico-Genomic Interrogation of Secondary-Type Acute Myeloid Leukemia: Response and Outcomes to Contemporary Therapies,” published in the February 2025 issue of American Journal of Hematology by Senapati et al.
Acute myeloid leukemia (AML) ontogeny holds prognostic value, but its impact on characteristics, genomics, and treatments needs further evaluation.
Researchers conducted a retrospective study to evaluate the prognostic impact of AML ontogeny on characteristics, genomics secondary (GS), and venetoclax-based treatment outcomes.
They classified newly diagnosed patients with AML as untreated CS-AML (n = 133) or GS-AML (n = 389). CS-AML had antecedent myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm (MDS-MPN) without prior hypomethylating agents or chemotherapy, while GS-AML had myelodysplasia-related cytogenetics (MRC) or myelodysplasia-related mutations (MRM) without prior myeloid neoplasm or chemo-radiotherapy. They analyzed relapse-free survival (RFS) and overall survival (OS) across treatment regimens, including low-intensity therapy (LIT) with venetoclax.
The results showed median RFS (11.9 vs. 12.4 months, P = 0.36) and OS (11.6 vs 14.4 months, P = 0.75) were similar between untreated CS-AML and GS-AML. No differences in RFS and OS were seen with LIT and venetoclax, but both had worse outcomes than pure de novo (DN)-AML. GS-AML with MRM alone had superior OS vs MRM ± MRC with LIT + venetoclax (RFS 19.5 vs 6.8 months, P < 0.01; OS 29.6 vs 8.4 months, P < 0.01) and similar RFS (29.8 months, P = 0.48) and OS (32.0 months, P = 0.48) to pure DN-AML with LIT + venetoclax. On multivariate analysis, untreated CS-AML, adverse cytogenetics, and ELN 2024 adverse-risk disease (mutated TP53) were linked to higher mortality risk, with adverse cytogenetics as the strongest predictor.
Investigators found that mutation-driven genomic ontogeny in AML with MRM was less prognostic than cytogenetic-driven ontogeny with venetoclax-based therapy.
Source: onlinelibrary.wiley.com/doi/10.1002/ajh.27628
