Researchers have designed and validated a simple, robust genetic model, the ALFA decision tool that is able to determine the prognosis for patients with acute myeloid leukemia (AML) ≥60 years of age who were treated with intensive chemotherapy. The report was published recently in Blood.
To design the model predicting overall survival (OS) of patients with AML and ≥60 years of age who were treated with 7+3, the team sequenced 37 genes in 471 patients from the Acute Leukemia French Association (ALFA) 1200 study. The median age of patients was 68 years (range, 60-85). Most patients (82.8%) had de novo AML.
Mutation patterns and OS differed between the patients with poor-risk cytogenetics (n=84; 17.8%) and those with good (n=13; 2.8%), intermediate (n=339; 72%), or unmeasured (n=35) cytogenetic risk. Mutations in TP53 (hazards ratio [HR], 2.49; P =.0003) and KRAS (HR, 3.60; P =.001) independently worsened OS in patients with poor-risk cytogenetics. In those with all other cytogenetic risks, mutations in NPM1 (HR, 0.57; P =.0004), FLT3 internal tandem duplications with low (HR, 1.85; P =.0005) or high (HR, 3.51; P <10-4) allelic ratio, DNMT3A (HR, 1.86; P <10-4), NRAS (HR, 1.54; P =.019), and ASXL1 (HR, 1.89; P =.0003) independently predicted OS.
For the model, the researchers combined cytogenetic risk and mutations in the 7 independently associated genes, and of the patients, 39.1% were classified to a “go-go” group (in whom 7+3 is unequivocally beneficial) with a 2-year OS of 66.1%; 3.3% to a “slow-go” group with a 2-year OS of 39.1%; and 7.6% to a “no-go” group (in whom 7+3 is futile) with a 2-year OS of 2.8% (P <10-5).
They then validated the tool using 3 independent cohorts, among which 31.2% to 37.7% and 11.2% to 13.5% of patients were assigned to the go-go and the no-go groups, respectively, and with significant differences in OS between the groups in all cohorts (Hauts-de-France cohort n=141; P =.003; StudyAlliance Leukemia cohort n=46; P <10-5; AML Study Group cohort n=223; P <10-5).
“[O]ur simple, reproducible, and discriminant decision tool has the potential to first instruct the design of future clinical trials in fit patients with AML, and then guide frontline treatment decisions in routine practice,” the authors wrote.
Itzykson RA, Fournier E, Berthon C, et al. Genetic identification of AML patients older than 60 years achieving long-term survival with intensive chemotherapy. Blood. Published online August 19, 2021. doi:10.1182/blood.2021011103