Gemtuzumab Ozogamicin Improves Event-Free Survival and Reduces Relapse in Pediatric <i>KMT2A</i> -Rearranged AML: Results From the Phase III Children's Oncology Group Trial AAML0531
Jessica A. Pollard, Erin Guest, Todd A. Alonzo, Robert B. Gerbing, Mike R. Loken, Lisa Eidenschink Brodersen, E. Anders Kolb, Richard Aplenc, Soheil Meshinchi, Susana C. Raimondi, Betsy Hirsch, Alan S. Gamis
Abstract
PURPOSE We investigated the impact of the CD33-targeted agent gemtuzumab ozogamicin (GO) on survival in pediatric patients with KMT2A-rearranged ( KMT2A-r) acute myeloid leukemia (AML) enrolled in the Children's Oncology Group trial AAML0531 ( NCT01407757 ). METHODS Patients with KMT2A-r AML were identified and clinical characteristics described. Five-year overall survival (OS), event-free survival (EFS), disease-free survival (DFS), and relapse risk (RR) were determined overall and for higher-risk versus not high-risk translocation partners. GO's impact on response was determined and outcomes based on consolidation approach (hematopoietic stem cell transplant [HSCT] v chemotherapy) described. RESULTS Two hundred fifteen (21%) of 1,022 patients enrolled had KMT2A-r AML. Five-year EFS and OS from study entry were 38% and 58%, respectively. EFS was superior with GO treatment (EFS 48% with GO v 29% without, P = .003), although OS was comparable (63% v 53%, P = .054). For patients with KMT2A-r AML who achieved complete remission, GO was associated with lower RR (40% GO v 66% patients who did not receive GO [No-GO], P = .001) and improved 5-year DFS (GO 57% v No-GO 33%, P = .002). GO benefit was observed in both higher-risk and not high-risk KMT2A-r subsets. For patients who underwent HSCT, prior GO exposure was associated with decreased relapse (5-year RR: 28% GO and HSCT v 73% No-GO and HSCT, P = .006). In multivariable analysis, GO was independently associated with improved EFS, improved DFS, and reduced RR. CONCLUSION GO added to conventional chemotherapy improved outcomes for KMT2A-r AML; consolidation with HSCT may further enhance outcomes. Future clinical trials should study CD33-targeted agents in combination with HSCT for pediatric KMT2A-r AML.