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.

Abstract

We investigated the impact of the CD33-targeted agent gemtuzumab ozogamicin (GO) on survival in pediatric patients with <i>KMT2A</i>-rearranged (<i>KMT2A</i>-r) acute myeloid leukemia (AML) enrolled in the Children's Oncology Group trial AAML0531 (NCT01407757). Patients with <i>KMT2A</i>-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] <i>v</i> chemotherapy) described. Two hundred fifteen (21%) of 1,022 patients enrolled had <i>KMT2A</i>-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 <i>v</i> 29% without, <i>P</i> = .003), although OS was comparable (63% <i>v</i> 53%, <i>P</i> = .054). For patients with <i>KMT2A</i>-r AML who achieved complete remission, GO was associated with lower RR (40% GO <i>v</i> 66% patients who did not receive GO [No-GO], <i>P</i> = .001) and improved 5-year DFS (GO 57% <i>v</i> No-GO 33%, <i>P</i> = .002). GO benefit was observed in both higher-risk and not high-risk <i>KMT2A</i>-r subsets. For patients who underwent HSCT, prior GO exposure was associated with decreased relapse (5-year RR: 28% GO and HSCT <i>v</i> 73% No-GO and HSCT, <i>P</i> = .006). In multivariable analysis, GO was independently associated with improved EFS, improved DFS, and reduced RR. GO added to conventional chemotherapy improved outcomes for <i>KMT2A</i>-r AML; consolidation with HSCT may further enhance outcomes. Future clinical trials should study CD33-targeted agents in combination with HSCT for pediatric <i>KMT2A-</i>r AML.