Venetoclax in combination with chemotherapy as treatment for pediatric advanced hematologic malignancies

Abstract Background Venetoclax is frequently used as salvage treatment in pediatric, adolescent, and young adult (AYA) patients with advanced hematologic malignancies. However, more data are needed from real‐world studies to guide the safe and appropriate use of venetoclax in this population. Procedure We retrospectively reviewed the medical records of all patients diagnosed with hematologic malignancies less than 30 years of age treated with venetoclax outside of clinical trials at the University of California San Francisco Benioff Children's Hospitals from 2016 to 2022. Results We identified 13 patients (acute myeloid leukemia , n = 8; B‐acute lymphoblastic leukemia, n = 3; myelodysplastic syndrome, n = 2) aged 4 months to 27 years. A median of 3 prior lines of therapy weregiven (range 0–5). All patients received venetoclax in combination with either a hypomethylating agent or conventional chemotherapy. Three (23%) patients achieved complete remission (CR); two (15%) achieved partial remission (PR); 3 (23%) had stable disease (SD), and five (42%) had progressive disease. Median survival and time to progression from venetoclax initiation was 9 months (range 2.5–52 months) and 3 months (range 2 weeks to 7.5 months), respectively. Six patients (46%) developed grade 3 or higher infections while receiving venetoclax, including bacteremia due to atypical organisms, invasive pulmonary infections with Aspergillus, cytomegalovirus (CMV) viremia, skin infections, and encephalitis with bacterial brain abscesses. Conclusions Venetoclax in combination with hypomethylating agents or cytotoxic chemotherapy was effective in a subset of pediatric/AYA patients with advanced hematologic malignancies, but multiple severe infections were observed, particularly among patients who received venetoclax in combination with chemotherapy. Prospective studies will be required to determine the optimal dose and duration of venetoclax in this population.