Risk stratification of LDAC + venetoclax in ND AML ineligible for IC

Results from a pooled, retrospective analysis of the phase Ib/II M14‑387 (NCT02287233) and phase III VIALE‑C (NCT03069352) trials, evaluating risk stratification in 139 patients with newly diagnosed (ND) acute myeloid leukemia (AML) treated with low-dose cytarabine (LDAC) + venetoclax and ineligible for intensive chemotherapy (IC), were published in Blood Advances by Wei et al. The primary objective of this analysis was to evaluate the applicability of The European LeukemiaNet (ELN) 2022 risk stratification criteria, or a 4‑gene classifier developed for azacitidine + venetoclax, as a prognostic tool for patients treated with LDAC + venetoclax.

Key data: Neither the ELN 2022 criteria nor the 4‑gene classifier adequately stratified outcomes in this population. Data-driven and empirical analyses identified that the absence of a complex karyotype defined a higher benefit group than presence of a complex karyotype, with a median overall survival (OS) of 16.4 months vs 3.4 months. Similarly, complete response (CR) and CR with incomplete blood count recovery (CRi) rates were greater among patients without vs with a complex karyotype (CR, 44% vs 3%; CRi, 23% vs 18%). Among patients lacking a complex karyotype, those with NPM1 variants demonstrated an OS of 29.7 months vs 12.9 months in those with wild-type NPM1. Of patients with a complex karyotype, 67% also harbored a TP53 mutation.

Key learning: Findings suggest that existing AML risk stratification tools are unable to adequately predict the prognosis of patients with ND AML unfit for IC, receiving LDAC + venetoclax. Complex karyotype represents the most clinically relevant adverse prognostic marker for this regimen, indicating a need for therapy-specific risk classification models.