...- AML with any adverse cytogenetics, TP53 mutation, RUNX1 mutation, ASXL1, 11q23/KMT2 rearrangements...

...- a history of mutation in TP53, RUNX1, or ASXL1...

CONTRADICTING EVIDENCE: This multicenter, single-arm, phase 2 trial (NCT04752527) enrolled young pts (aged between 18 and 59) with ND AML...Pts harboring TP53 and ASXL1 mutations achieved encouraging CRc rates of 62.5% and 75%, respectively.

CONTRADICTING EVIDENCE: In this study, we aimed to evaluate the efficacy of VEN combined with hypomethylating agents (HMA) and identify the potentially predictive factors for response in R/R AML....Mutations in IDH1/2, NPM1 and ASXL1 predicted superior response to VEN-based therapy (CRc: 78.3%, 70.8% and 65.0%, respectively), while mutations in active signaling, such as FLT3-ITD, K/NRAS predicted inferior response (CRc: 29.0% and 28.6%).

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).

CONTRADICTING EVIDENCE: With a median follow-up of 11.2 (95%CI, 7.2-14.8) months, 1- and 2-year overall survival were 46.9% (95% CI, 37.8%-58.1%) and 38.9% (95% CI, 28.7%-52.9%), respectively…Mutations in IDH1/2, NPM1, ASXL1 and chromatin-cohesin genes predicted superior response to VEN-based therapy, whereas mutations in active signaling genes such as FLT3-ITD and K/NRAS predicted inferior response...VEN combined with HMA was effective with R/R AML patients, and the response to treatment was associated with genetic characteristics.

CONTRADICTING EVIDENCE: 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.

CONTRADICTING EVIDENCE: This retrospective study included consecutive patients treated with VEN-AZA for R/R AML and ND AML....ASXL1, IDH1/2 and SRSF2 mutations were associated with a trend in a higher response rate in the R/R group.

CONTRADICTING EVIDENCE: 103 AML patients (median age 74 years, 67% male, 62% de novo) received upfront Ven + HMA....In univariate analysis, presence of ASXL1 mutation was associated with favorable response (CR/CRi 83% vs 53%, p=0.01), secondary AML (CR/CRi 49% vs 65%, p=0.09), adverse karyotype (49% vs 67%, p=0.11), presence of TP53 (32% vs 67%, p=0.002) and FLT3-ITD mutations (30% vs 61%; p=0.06) predicted inferior response.

DEC10-VEN is an effective regimen for AML. Addition of FLT3i to DEC10-VEN was safe and may improve upon responses in FLT3mut pts. Mutations in NPM1 and DNA methylation pathways were associated with more durable responses while mutations in ASXL1, RAS and TP53 were associated with refractory disease or relapse.