Venetoclax plus modified-intensity Idarubicin and Cytarabine treatment as first-line treatment for newly diagnosed pediatric acute myeloid leukemia

Abstract Purpose: Venetoclax (VEN) has shown excellent activity in eliminating acute myeloid leukemia (AML) blasts in preclinical and clinical trials, but clinical data in pediatric newly diagnosed AML (ND-AML) remain limited. We evaluated VEN plus modified-intensity idarubicin and cytarabine chemotherapy (VIA) in childhood ND-AML. Experimental design: In an open-label, single-arm, multi-center prospective clinical trial, 65 ND-AML pediatric patients received VIA induction (VEN and modified-intensity cytarabine and idarubicin). Consolidation was guided on response to induction and individualized risk stratification. Primary end point was complete remission (CR) and measurable residual disease (MRD) response rates. Results: After induction cycle 1, CR and MRD negativity was 90.8% and 78.5%, increasing to 96.8% and 87.3% following induction cycle 2. 28 (43.2%) patients underwent hematopoietic stem cell transplantation (HSCT) without engraftment failure. CBF AML [t(8;21) and inv(16)/t(16;16)] patients achieved a favorable response rate, but the median log10 reduction of transcript levels was suboptimal [-1.7 (cycle 1) and -2.6 (cycle 2) for RUNX1::RUNX1T1, -2.3 and -2.5 for CBFB::MYH11]. Disease relapse was frequently observed in KIT mutation, RUNX1::RUNX1T1 and CBFB::MYH11. The most common grade 3-4 toxicities were hematological toxicities and febrile neutropenia (FN). No treatment-related deaths occurred. With a median follow-up of 15.7 months, the estimated 12-month overall survival and event-free survival was 92.3% (95% CI 86.0-99.8) and 79.1% (95% CI 69.6-90.0). MRD negativity post cycle 1 correlated with superior long-term survival (P < 0.001). Conclusions: VIA regimen is highly effective and relatively safe in children with ND-AML, with deep remission and favorable survival outcomes.