Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531

• Published in: Journal of clinical oncology Vol. 32; no. 27; pp. 3021 - 3032
• Main Authors: Gamis, Alan S, Alonzo, Todd A, Meshinchi, Soheil, Sung, Lillian, Gerbing, Robert B, Raimondi, Susana C, Hirsch, Betsy A, Kahwash, Samir B, Heerema-McKenney, Amy, Winter, Laura, Glick, Kathleen, Davies, Stella M, Byron, Patti, Smith, Franklin O, Aplenc, Richard
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 20.09.2014
• Subjects: Adolescent; Adult; Aminoglycosides - therapeutic use; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Canada - epidemiology; Child; Child, Preschool; Disease-Free Survival; Female; Humans; Induction Chemotherapy - methods; Infant; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - mortality; Male; ORIGINAL REPORTS; Recurrence; Stem Cell Transplantation; Treatment Outcome; United States - epidemiology; Young Adult
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2014.55.3628

To improve survival rates in children with acute myeloid leukemia (AML), we evaluated gemtuzumab-ozogamicin (GO), a humanized immunoconjugate targeted against CD33, as an alternative to further chemotherapy dose escalation. Our primary objective was to determine whether adding GO to standard chemotherapy improved event-free survival (EFS) and overall survival (OS) in children with newly diagnosed AML. Our secondary objectives examined outcomes by risk group and method of intensification. Children, adolescents, and young adults ages 0 to 29 years with newly diagnosed AML were enrolled onto Children’s Oncology Group trial AAML0531 and then were randomly assigned to either standard five-course chemotherapy alone or to the same chemotherapy with two doses of GO (3 mg/m2/dose) administered once in induction course 1 and once in intensification course 2 (two of three). There were 1,022 evaluable patients enrolled. GO significantly improved EFS (3 years: 53.1% v. 46.9%; hazard ratio [HzR], 0.83; 95% CI, 0.70 to 0.99; P.04) but not OS (3 years: 69.4% v. 65.4%; HzR, 0.91; 95% CI, 0.74 to 1.13; P = .39). Although remission was not improved (88% v. 85%; P = .15), posthoc analyses found relapse risk (RR) was significantly reduced among GO recipients overall (3 years: 32.8% v. 41.3%; HzR, 0.73; 95% CI, 0.58 to 0.91; P = .006). Despite an increased postremission toxic mortality (3 years: 6.6% v. 4.1%; HzR, 1.69; 95% CI, 0.93 to 3.08; P = .09), disease-free survival was better among GO recipients (3 years: 60.6% v. 54.7%; HzR, 0.82; 95% CI, 0.67 to 1.02; P = .07). GO added to chemotherapy improved EFS through a reduction in RR for children and adolescents with AML.