Background: VEN-based low intensity regimens have shown promise in older pts with newly diagnosed (ND) AML. We hypothesized that adding VEN to 10-day (d) DEC may improve outcomes in AML and HR MDS. Methods: Pts received VEN 400 mg daily or equivalent with DEC 20 mg/m² for 10d every 4-8 weeks for induction and DEC 5d with VEN for consolidation after CR/CRi. If cycle 1 day 21 bone marrow showed ≤5% blasts, VEN was held to enable count recovery. VEN duration could be further reduced for myelosuppression. FLT3 and IDH inhibitors were allowed for applicable pts. All pts received tumor lysis syndrome (TLS) prophylaxis. Primary objective was overall response rate (ORR). Secondary objectives were safety and overall survival (OS). Data cut-off date was February 6, 2020. Results: Between January 2018 and December 2019 we enrolled 184 pts with ND AML (>60 yrs), untreated secondary AML (sAML), treated sAML, relapsed/refractory (R/R) AML and HR MDS (Table). 58% pts were ≥70 yrs, 30% pts had ECOG PS ≥2, 67% pts had ELN adverse risk AML. Previously treated pts (n=96) had received a median of 1 prior therapy (range 1-8) including HMA (62), intensive chemotherapy (49) and stem cell transplantation (SCT, 27). 30d mortality was 3.3% and 60d mortality was 7.6%. 30d mortality in ND AML was 1.4%. Most common G3/4 adverse events were infections with G3/4 neutropenia (46%), febrile neutropenia (28%), infections with ANC ≥1x10⁹/L (6%) and TLS (3%). Outcomes are shown in Table. 25 pts (14%) proceeded to SCT including treatment naive AML (ND+ untreated sAML, 12), previously treated AML (treated sAML + R/R, 11) and HR MDS (2). 100d post-SCT mortality was 4%. Median OS in treatment naïve AML pts undergoing SCT was not reached (1yr OS 100%) and for previously treated AML pts was 22.1 months (mo). After a median follow up of 15 mos, 25% PTS continue therapy. Additional analyses by molecular subgroups will be presented. Conclusions: DEC10-VEN is safe and highly effective in ND AML and can serve as an effective bridge to SCT in previously treated pts. Trial continues to accrue (NCT03404193). Clinical trial information: NCT03404193.

3 more pts with untreated HR MDS achieved marrow CR (mCR) ongoing for a median of 5 mo

ORR = CR+CRi+MLFS+PR for AML and CR+mCR+PR+stable disease for MDS per IWG criteria