TY - JOUR
T1 - Gemtuzumab Ozogamicin Improves Event-Free Survival and Reduces Relapse in Pediatric KMT2A-Rearranged AML
T2 - Results From the Phase III Children’s Oncology Group Trial AAML0531
AU - Pollard, Jessica A.
AU - Guest, Erin
AU - Alonzo, Todd A.
AU - Gerbing, Robert B.
AU - Loken, Mike R.
AU - Brodersen, Lisa Eidenschink
AU - Anders Kolb, E.
AU - Aplenc, Richard
AU - Meshinchi, Soheil
AU - Raimondi, Susana C.
AU - Hirsch, Betsy
AU - Gamis, Alan S.
N1 - Publisher Copyright:
Copyright © 2022 American Society of Clinical Oncology. All rights reserved.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - 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 5 .003), although OS was comparable (63% v 53%, P 5 .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 5 .001) and improved 5-year DFS (GO 57% v No-GO 33%, P 5 .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 5 .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.
AB - 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 5 .003), although OS was comparable (63% v 53%, P 5 .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 5 .001) and improved 5-year DFS (GO 57% v No-GO 33%, P 5 .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 5 .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.
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U2 - 10.1200/JCO.20.03048
DO - 10.1200/JCO.20.03048
M3 - Article
C2 - 34048275
AN - SCOPUS:85113328960
SN - 0732-183X
VL - 39
SP - 3149
EP - 3160
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 28
ER -