The BCL2 inhibitor venetoclax has become a common treatment for some types of leukemias and lymphomas, but use of this agent in pediatric patients is relatively rare. A phase I dose-finding study published in Lancet Oncology evaluated the combination of venetoclax with high-dose cytarabine, with or without idarubicin, in 38 patients aged 3 to 22 years of age with relapsed/refractory acute myeloid leukemia (AML) to determine if this agent is safe and active in a pediatric population.
At a median follow-up of 7.1 months, the objective response rate (ORR) across all doses and schedules evaluated was 69%, including complete response in 46% of patients and complete response with incomplete hematologic recovery in 11% of patients. A dose of 360 mg/m2 of venetoclax (combined with 8 cycles of cytarabine 1000 mg/m2 and an optional single dose of idarubicin 12 mg/m2) was identified as optimal for future study. Among 20 evaluable patients who received this dose, the ORR was 80%, with 70% of patients achieving a complete response with or without complete hematologic recovery.
The adverse events (AEs) were generally consistent with the known safety profiles of venetoclax and high-dose cytarabine. The most common grade 3/4 AEs were febrile neutropenia and infections. One patient died due to treatment-related colitis and sepsis.
The authors concluded that venetoclax plus intensive chemotherapy is safe and active in pediatric patients with relapsed/refractory AML and may represent a treatment alternative for this difficult-to-treat population. The phase II portion of this study is currently ongoing, and studies evaluating venetoclax as a frontline treatment option are planned.
Read more about this article on Lancet Oncology.