Expansion seen w/in first 14d. Toxicities most commonly hematologic (febrile neutropenia) & infection. G1-2 fevers in 7/20 w/o severe CRS. 50% ORR (39% CR/CRh, all MRD neg). Longest responses >1y. Dose expansion ongoing at 1.5x10^9 million on day 0/7/14. (2/2) #ASH25

Cytopenias common as below w/ improvement on disease clearance. ORR 67% (CR/CRi 64%). Median DOR 9.7 months. Consolidative alloHCT assoc w/ better DOR/OS. TENACITY-01 study in US ongoing. (2/2) #ASH25

2/11 G3+ CRS, 3/11 ICANS, 10/11 transient rash, G4 hematotox and viremia in all. All had expansion in PB by ddPCR. All CRi; "deep" in 9/11. 7/11 alive in CR after alloHCT. NEJM publication out today (www.nejm.org/doi/full/10....). (2/2) #ASH25

Interestingly, one pt developed donor-derived AML, rapidly progressive. Overall, encouraging that all pts achieved MRD-neg CRi and most were able to be bridged to alloHCT. Peri-transplant shock and disease relapse remain concerns. #ASH25 (2/2)

G3 CRS in 10% and 2/30 developed ICANS. All responded in CNS and 22/24 had MRD-neg CR in marrow; lower but strong resp rates for EMD. 18/24 CR pts proceeded to alloHCT consolidation. Encouraging long-term follow-up through small N. (2/2) #ASH25

*2 weeks median

18% overall w/ G2+ LV systolic dysfunction. No sig benefit w/ ACEi before LV systolic dysfunction but possible protective effect w/ earlier initiation. (2/2) #ASH25

Incidence of CNS decreased to 18% and lower incidence of CNS relapse. Inferior relapse w/ CNS3 disease driven at least in part by CNS relapse. AlloHCT also ↓ risk of CNS relapse. (2/2) #ASH25

Better outcomes as expected in those achieving CR/CRi or getting to alloHCT. Ven didn't improve OS/EFS either. Remains a challenging pt population to treat; oral decitabine may be attractive for some as well given lack of advantage for aza. (2/2) #ASH25

Risk factors (HTN, tobacco, HLD, etc) balanced w/ propensity score matching. 13.1 vs 9.2% HF (6.9 vs 3.5% HFrEF) w/ dauno vs ida. All cause mortality similar. Cardiac-related mortality not assessed. (2/2) #ASH25

Relative and absolute BMA blast reduction from baseline to day 14 was not associated significantly w/ CR post-reinduction, or w/ DFS/OS. Reason for pursuing reinduction (or not) isn't available and doesn't compare different strategies. Will be good to compare w/ those not reinduced. (2/2) #ASH25

Certain risk factors for BM relapse (age, female sex) did NOT predict CNS relapse. CNS status at dx predictive of CNS but not BM relapse. EOI MRD, unfavorable genetics, specific race/ethnic groups (see linked figure), associated w/ both CNS and BM relapse. (2/2) #ASH25

89% CR; MRD responses as below. 17% rec'd TKI. Non-NUP214::ABL1 had 15% vs 5% rate of induction failure. 5y EFS 78% overall, numerically better w/ NUP214::ABL1. No clear benefit to TKI in non-BCR::ABL1, but small N. alloHCT in CR1 assoc w/ ↑EFS. (2/2) #ASH25