LAUSR

Outcomes of older and un fi t adults with acute myeloid leukemia (AML) differ signi fi cantly from their younger counterparts, owing to their adverse disease biology (complex karyotype, antecedent myelo-dysplastic syndrome) and age-related comorbidities. 1 Recently, venetoclax-based lower intensity therapies were approved for newly diagnosed (ND) AML in older (aged ≥ 75 years) adults and/or those not eligible for intensive chemotherapy. 2,3 However, given the lack of consensus on the de fi nition of eligibility criteria for intensive chemotherapy in older age, intensive chemotherapy continues to be used under the assumption that lower intensity therapies may sacri fi ce ef fi cacy for tolerability. 4 We evaluated 248 older and un fi t patients with ND non – core-binding-factor AML treated on 2 clinical trials investi-gating double nucleoside-analog therapy (DNT) alternating with decitabine and demonstrated a composite complete remission (CRc) rate of 66% with a median overall survival (OS) of 12.5 months. The 4- and 8-week mortality rates were 2% and 11%, respectively. In a longer follow-up, we con fi rm that low-intensity DNT regimens led to higher response rates, durable remissions, and improved OS compared with our historical experience with hypomethylating agents. 5 In a recent prognostic model incorporating karyotypic abnormalities and 7 recurrently mutated genes in AML, the Acute Leukemia French Association (ALFA) 1200 study investigators identi fi ed and validated a genomic score that effectively classi fi ed patients with ND AML aged ≥ 60 years into 3 distinct prognostic