Venetoclax (BCL-2 inhibitor) + high-dose cytarabine drives 57% CR/CRi in pediatric R/R AML (VENAML)

VENAML tested venetoclax, an oral BCL-2 inhibitor that restores mitochondrial apoptosis priming, combined with high-dose cytarabine (± idarubicin/dexrazoxane or azacitidine) in a multicentre Phase 1 expansion in children/AYA (age 2–24) with relapsed/refractory AML treated at the RP2D (n=44; 3 US hospitals; NCT03194932). After 1 cycle, composite CR (CR±hematologic recovery) was 57% (25/44; 95% CI 41–72) with 19 MRD-negative responses—numerically in the range of common intensive salvage backbones like FLAG±IDA reported around ~50–70% CR in pediatric/AYA series, but achieved here with a venetoclax-based platform intended to be a bridge to transplant rather than “more of the same” cytotoxic escalation. Grade 3/4 toxicity was dominated by expected myelosuppression/infection signals—febrile neutropenia 52%, GI disorders 32% (colitis 9%), infections 25%—with 2 grade 5 events (sepsis and multiorgan failure), underscoring that “acceptable” still means ICU-level risk in this setting.