...Time to CR/CRi`Time to minimal residual disease (MRD) negativity`Overall survival (Arm A vs Arm B)`Progression-free survival`Overall survival (patients with DNMT3A mutations vs patients with wild-type DNMT3A)`Rate of adverse events...

A total of 89 AML cases registered in HLN from May 2021 to April 2023 were initially treated by VEN-based therapy....Furthermore, the ratio of CR or CRi was more than 80% in the patients with mutation of CEBPA-bZIP, DNMT3A, IDH1, IDH2, and NPM1 mutation-positive groups, respectively.

Patients with TET2 (P=0.041), NPM1 (P=0.039), ASXL1 (P=0.044), FLT3-ITD/TKD (P=0.008), DNMT3A (P<0.001) or RAS (P=0.006) mutation or co-mutation of DNMT3A and FLT3 (P=0.020, DNMT3A and NPM1 (P=0.020) or DNMT3A and IDH/2 (P=0.016) acquired statistically higher rate of CR/CRi with VAH therapy as compared with VEN+HMA trerapy....AML1-ETO-positive AML patients poorly responded to VEN+HMA therapy (0/7), but responded much better to VAH treatment (5/7, P=0.005).

The median age is 75 years (range, 46-92); 73 in the FL cohort and 75.5 in the R/R cohort...Mutations of note in the frontline cohort were TET2 (35%), ASXL1 (30%), RUNX1 (24%), TP53 (16%), and DNMT3A (11%)...In the R/R cohort, the overall response rate is 53% (6 CR, 1 CRi, 1 MLFS with 7 non-responders). Both cohorts received a median of 3 cycles (range for both cohorts, 1-8). With a median follow-up of 7 months, the median survival for the FL cohort is 9.5 months (range, 0.6 – 11.1)...ASTX727 and venetoclax combination is safe and feasible particularly in the advanced elderly population and demonstrates significant efficacy in pts unfit for chemotherapy both in the FL and R/R settings. Total oral therapy of ASTX727 and venetoclax combination appears to be a promising strategy for older and unfit patients with AML.

ASTX727 is administered daily on days 1‐5 of each cycle and ven on days 1‐28 of the first cycle after a dose ramp up of 100-200-400 mg over 3 days...Mutations of note in the frontline cohort were RUNX1 (33%), ASXL1 (33%), DNMT3A (7%), TET2 (40%) and TP53 (20%). The overall response rate (ORR) including complete response (CR), CR with incomplete count recovery (CRi) and morphological leukemia free state (MLFS) in the FL cohort is 61% (4 CR, 4 CRi, 1 MLFS and 3 non-responders)...Total oral therapy of ASTX727+ven is safe and feasible, particularly in the advanced elderly population, and demonstrates significant efficacy in pts unfit for chemotherapy both in the FL and R/R settings.

All AML pts who received treatment with aza/ven, dec/ven or LDAC/ven as either initial induction or for RR disease...A total of 130 pts were treated with ven combo therapy with 18 pts (13.8% of all pts) receiving a subsequent alloSCT. While pts with DNMT3A, NPM1, IDH1/2 and FLT3 mutations had a high response rate to ven therapy...Only DNMT3A mutations were statistically significantly associated with a high response rate prior to alloSCT (ORR 100%, CR/CRi 63%, p=0.01).