Data from Gemtuzumab Ozogamicin Reduces Relapse Risk in <i>FLT3</i>/ITD Acute Myeloid Leukemia: A Report from the Children's Oncology Group

Abstract

<div>Abstract<p><b>Purpose:</b> Gemtuzumab ozogamicin (GO), a calicheamicin-conjugated mAb against CD33, has been used in the treatment of acute myeloid leukemia (AML). We evaluated the impact of the addition of GO to standard chemotherapy and hematopoietic stem cell transplant (HCT) in patients with <i>FLT3</i>/ITD.</p><p><b>Experimental Design:</b> We analyzed children with <i>FLT3</i>/ITD–positive AML (<i>n</i> = 183) treated on two consecutive Children's Oncology Group AML trials (NCT00070174 and NCT00372593). Outcomes were assessed for <i>FLT3</i>/ITD patients receiving standard chemotherapy with or without GO (GO vs. No-GO, respectively), and the impact of consolidation HCT for high-risk <i>FLT3</i>/ITD patients [high <i>FLT3</i>/ITD allelic ratio (ITD-AR)].</p><p><b>Results:</b> For all <i>FLT3</i>/ITD patients, complete remission (CR) rates for the GO versus No-GO cohorts were identical (64% vs. 64%; <i>P</i> = 0.98). Relapse rate (RR) after initial CR was 37% for GO recipients versus 59% for No-GO recipients (<i>P</i> = 0.02), disease-free survival (DFS) was similar (47% vs. 41%; <i>P</i> = 0.45), with higher treatment-related mortality (TRM) in GO recipients (16% vs. 0%; <i>P</i> = 0.008). Among high-risk <i>FLT3</i>/ITD patients with high ITD-AR, those who received HCT in first CR with prior exposure to GO had a significant reduction in RR (15% vs. 53%; <i>P</i> = 0.007), with a corresponding DFS of 65% versus 40% (<i>P</i> = 0.08), and higher TRM (19% vs. 7%; <i>P</i> = 0.08).</p><p><b>Conclusions:</b> CD33 targeting with HCT consolidation may be an important therapeutic strategy in high-risk <i>FLT3</i>/ITD AML and its efficacy and associated toxicity warrant further investigation. <i>Clin Cancer Res; 22(8); 1951–7. ©2015 AACR</i>.</p></div>