Clinical activity of venetoclax and azacitidine in children with de novo or secondary multiple relapsed/refractory acute myeloid leukemia: a real-world experience

Acute myeloid leukemia (AML) remains a major therapeutic challenge, particularly in relapsed or refractory patients, where prognosis is poor. The combination of venetoclax and azacitidine (ven/aza) has demonstrated significant efficacy in adults, yet evidence in pediatric populations is still limited and warrants further investigation. We conducted a multi-center retrospective analysis of 38 pediatric patients with relapsed/refractory (R/R) AML, including patients with de novo and secondary AML, treated with compassionate use ven/aza in four European countries between 2017 and 2023. Patient characteristics, AML-associated genetic alterations, treatment details, clinical responses, and adverse events with ven/aza therapy were analyzed. Among 38 children with R/R AML treated with ven/aza, the composite response rate (complete remission or complete remission with incomplete count recovery) was 26.3%. Median progression-free survival in responding patients was 22 months, and overall survival for the cohort was 6.1 months. Common ≥grade 3 toxicities included cytopenias (94%) and positive blood cultures (29%). This study demonstrates the real-world efficacy and tolerability of ven/aza in pediatric R/R AML. The regimen enabled remission and prolonged survival in select cases, with manageable toxicity and improved outpatient care. Findings support the need for pediatric trials to clarify therapeutic potential and identify predictive biomarkers.