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Acute Myeloid Leukemia
Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children’s Oncology Group
Richard Aplenc,1 Soheil Meshinchi,2* Lillian Sung,3* Todd Alonzo,4 John Choi,5 Brian Fisher,6 Robert Gerbing,7 Betsy Hirsch,8 Terzah Horton,9
Samir Kahwash,10 John Levine,11 Michael Loken,12 Lisa Brodersen,12
Jessica Pollard,13 Susana Raimondi,5 Edward Anders Kolb14 and Alan Gamis15
1The Children’s Hospital of Philadelphia, Division of Oncology, Philadelphia, PA, USA; 2Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 3The Hospital for Sick Children, Toronto, ON, Canada; 4University of Southern California, Los Angeles, CA, USA; 5St. Jude Children's Research Hospital, Memphis, TN, USA; 6The Children’s Hospital of Philadelphia, Division of Infectious Disease, Philadelphia, PA, USA; 7Children's Oncology Group, Monrovia, CA, USA; 8University of Minnesota, Minneapolis, MN, USA; 9Texas Children’s Hospital, Houston, TX, USA; 10Nationwide Children's Hospital, Columbus, OH, USA; 11Mount Sinai Medical Center, New York, NY, USA; 12Hemaologics Inc., Seattle, WA, USA; 13Dana Farber Cancer Center, Boston, MA, USA; 14Alfred I. duPont Hospital for Children, Wilmington, DE, USA and 15Children's Mercy Hospital and Clinics, Kansas City, MO, USA
ABSTRACT
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 hematopoiet- ic 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, borte- zomib 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 chil- dren with de novo AML. (Trial registered at clinicaltrials.govNCT01371981; https://www.cancer.gov/clinicaltrials/ NCT01371981).
Introduction
Pediatric acute myeloid leukemia (AML) is the second most common pediatric leukemia and requires intensive therapy for cure.1,2 Despite the intensity of AML chemotherapy, which includes a very high cumulative lifetime anthracycline expo- sure in patients treated with chemotherapy alone or allogeneic donor stem cell transplantation (SCT) in first remission, approximately 50% of patients will experi-
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Haematologica 2020 Volume 105(7):1879-1886
*RA and SM contributed equally to this work.
Correspondence:
RICHARD APLENC
aplenc@email.chop.edu
Received: March 7, 2019. Accepted: February 5, 2020. Pre-published: February 6, 2020.
doi:10.3324/haematol.2019.220962
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/7/1879
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