Venetoclax plus Modified-Intensity Idarubicin and Cytarabine Treatment as First-Line Treatment for Newly Diagnosed Pediatric Acute Myeloid Leukemia.

Abstract

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. In an open-label, single-arm, multicenter prospective clinical trial, 65 pediatric patients with ND-AML received VIA induction. Consolidation was guided on response to induction and individualized risk stratification. Primary end point was complete remission and measurable residual disease (MRD) response rates. After induction cycle 1, complete remission and MRD negativity was 90.8% and 78.5%, increasing to 96.8% and 87.3% following induction cycle 2. A total of 28 (43.2%) patients underwent hematopoietic stem cell transplantation without engraftment failure. Patients with core-binding factor (CBF) AML [t(8;21) and inv(16)/t(16;16)] 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 and -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 to 4 toxicities were hematologic toxicities and febrile neutropenia. 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% confidence interval, 86.0-99.8) and 79.1% (95% confidence interval, 69.6-90.0). MRD negativity after cycle 1 correlated with superior long-term survival (P < 0.001). The VIA regimen is highly effective and relatively safe in children with ND-AML, with deep remission and favorable survival outcomes observed.