Single‐center pediatric experience with venetoclax and azacitidine as treatment for myelodysplastic syndrome and acute myeloid leukemia

Abstract Background The BCL‐2 inhibitor venetoclax (ven) has revolutionized the treatment of acute myeloid leukemia (AML) in elderly adults, leading to its recent FDA approval for this population in combination regimens. Although extensive data exist for adult myeloid malignancies, there are limited preclinical data on the efficacy and/or dosing of venetoclax for pediatric myelodysplastic syndrome (MDS) or AML and thus little information to guide use of this regimen in pediatric patients. Our objective was to describe our single‐center experience with venetoclax in combination with the hypomethylating agent 5‐azacitidine (aza) in pediatric patients with MDS or AML. Procedure We conducted a retrospective chart review of patients treated at Children's Hospital Colorado prior to March 2020 with at least one cycle of ven/aza. Patients were included if between the ages of 1 and 25 years with a diagnosis of high‐grade MDS or AML. AML patients had relapsed or primary refractory disease or were deemed poor candidates for standard chemotherapy. Results Eight patients received ven/aza, two for high‐grade MDS and six for AML. Ven/aza was well tolerated by all patients. The most common adverse events seen with this regimen were gastrointestinal and hematologic. Morphologic responses were seen in six patients including both patients with MDS. All four AML responders became minimal residual disease negative. Three responders have thus far proceeded to allogeneic hematopoietic stem cell transplant following ven/aza. Conclusions Our clinical experience suggests that ven/aza is a safe and promising regimen that should be further explored with late‐phase clinical trials.