Acute myeloid leukemia (AML) is a highly heterogeneous clonal malignancy, accounting for approximately 15–20% of pediatric leukemia cases. The current standard first-line induction regimen, known as "3+7," achieves complete remission (CR) rates of approximately 70%. However, about 25% of pediatric patients eventually progress to relapsed/refractory AML (R/R AML), associated with poor prognosis.Venetoclax (VEN), a highly selective BCL-2 inhibitor, has demonstrated promising efficacy in adult AML and is recommended by both domestic and international guidelines as a first-line treatment option for elderly or chemotherapy-intolerant patients. In pediatric AML, while some studies have explored the feasibility of VEN combined with hypomethylating agents (HMAs) or intensive chemotherapy for R/R AML, systematic studies evaluating its efficacy and safety as first-line therapy for newly diagnosed AML (ND-AML) in children remain lacking.
Recently, Dr. Xiaofan Zhu from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, in collaboration with multiple centers across China, conducted a prospective multicenter clinical study investigating venetoclax combined with a reduced-intensity IA regimen (idarubicin plus cytarabine), termed the VIA regimen, in pediatric ND-AML. The study, titled “Venetoclax plus modified-intensity Idarubicin and Cytarabine treatment as first-line treatment for newly diagnosed pediatric acute myeloid leukemia”, was published in Clinical Cancer Research (IF=10.4). This is the first study to demonstrate both significant clinical efficacy and favorable safety of venetoclax-based reduced-intensity chemotherapy in children with newly diagnosed AML.
The VIA-pAML-2023 study (ChiCTR2300067686) is a prospective, multicenter clinical trial systematically evaluating the efficacy and safety of the VIA regimen in pediatric ND-AML, while exploring its clinical application in this population. A total of 65 pediatric ND-AML patients were enrolled. The VIA induction regimen included venetoclax administered orally at body weight-adjusted doses on days 4–11 (with a 50% dose reduction on day 4 during the first cycle), cytarabine (Ara-C) 200 mg/m² on days 1–5, and idarubicin (IDA) 8 mg/m² on days 1–3. Following induction therapy, patients underwent dynamic risk stratification and group adjustment using the CAMS-pAML network calculator and induction response data to guide subsequent individualized consolidation treatment.
The primary study endpoints were CR and minimal residual disease (MRD) negativity following induction therapy. Secondary endpoints included safety, event-free survival (EFS), and overall survival (OS). After the first VIA induction cycle, CR and MRD negativity rates reached 90.8% and 78.5%, respectively, improving to 96.8% and 87.3% after the second induction cycle. Among 28 intermediate- and high-risk patients (43.2%), hematopoietic stem cell transplantation (HSCT) was successfully performed, with no significant increase in transplant-related complications observed.
Safety analysis showed that Grade 3–4 adverse events were primarily hematologic toxicities and febrile neutropenia (FN), with no treatment-related deaths reported. At a median follow-up of 15.7 months, the 12-month OS and EFS rates were 92.3% (95% CI: 86.0–99.8) and 79.1% (95% CI: 69.6–90.0), respectively.
In conclusion, the VIA regimen demonstrated significant efficacy and favorable safety in pediatric patients with newly diagnosed AML, achieving deep remission and favorable survival outcomes.
