New therapeutic strategies are needed for pediatric
acute myeloid leukemia (AML) to reduce disease recurrence and treatment-related morbidity. The Children's Oncology Group Phase III AAML1031 trial tested whether the addition of
bortezomib to standard
chemotherapy improves survival in pediatric patients with newly diagnosed AML. AAML1031 randomized patients younger than 30 years of age with de novo AML to standard treatment with or without
bortezomib. All patients received the identical
chemotherapy backbone with either four intensive
chemotherapy courses or three courses followed by allogeneic
hematopoietic stem cell transplantation for high-risk patients. For those randomized to the intervention arm,
bortezomib 1.3 mg/m2 was given on days 1, 4 and 8 of each
chemotherapy course. For those randomized to the control arm,
bortezomib was not administered. In total, 1,097 patients were randomized to standard
chemotherapy (n=542) or standard
chemotherapy with
bortezomib (n=555). There was no difference in
remission induction rate between the
bortezomib and control treatment arms (89% vs 91%, P=0.531).
Bortezomib failed to improve 3-year event-free survival (44.8±4.5% vs 47.0±4.5%, P=0.236) or overall survival (63.6±4.5 vs 67.2±4.3, P=0.356) compared with the control arm. However,
bortezomib was associated with significantly more
peripheral neuropathy (P=0.006) and intensive care unit admissions (P=0.025) during the first course. The addition of
bortezomib to standard
chemotherapy increased toxicity but did not improve survival. These data do not support the addition of
bortezomib to standard
chemotherapy in children with de novo AML. (Trial registered at clinicaltrials.gov NCT01371981; https://www.
cancer.gov/clinicaltrials/ NCT01371981).