Improving the molecular risk classification for younger (<60 years) de novo cytogenetically normal acute myeloid leukemia (CN AML) patients (pts)

Abstract

7002 Background: CN AML pts are currently stratified into Low-risk [FLT3-ITD negative (neg)/NPM1 mutated (mut)] and High-risk [FLT3-ITD positive (pos) or NPM1 wild type (wt)] groups (FLT3-ITD/NPM1-only classification). We recently showed that low ERG expression and CEBPAmut identify pts with better outcome within, respectively, the Low- and High-risk groups, and that WT1mut confers poor outcome regardless of FLT3-ITD/NPM1 status. Here, we assess if adding CEBPA and WT1 mutation and ERG expression testing improves the currently used CN AML molecular risk classification. Methods: FLT3, NPM1, CEBPA and WT1 mutations and ERG and BAALC expression were tested at diagnosis in 143 CN AML adults enrolled on CALGB treatment protocols 9621 and 19808. Pts were divided into two molecular risk groups: i) CALGB Group I that included Low-risk pts with low ERG & High-risk pts with CEBPAmut and ii) CALGB Group II that included WT1mut pts & Low-risk pts with high ERG & High- risk pts with CEBPAwt. Results: CALGB Group I (n=56) v Group II (n=87) had more complete remissions (CRs) (P=.005; 96% v 79%), and longer disease-free (DFS; P<.0001; 5 year (y) 69% v 21%) and overall (OS; P<.0001; 5 y 70% v 31%) survival [median follow-up for pts alive 6 y]. In multivariable (MV) analyses, Group I predicted higher rate of CR (P=.02), and longer DFS (P<.0001) and OS (P=.0002), after correcting for other variables (Table). In contrast, for the same cohort of pts grouped by the FLT3-ITD/NPM1-only classification, CRs were 94% v 82% and 5 y DFS 59% v 32% and OS 67% v 36% in the Low- v High-risk groups. Based on the Akaike Information Criterion, MV models for DFS and OS using the CALGB risk Groups were better than those using the FLT3-ITD/NPM1-only risk groups. Conclusions: Prognostic classification of younger de novo CN AML pts is improved by adding CEBPA and WT1 mutation and ERG expression testing. While mutational analyses are ready for use in clinical trials, quantification of ERG expression is yet to be standardized. [Table: see text] No significant financial relationships to disclose.