Gemtuzumab ozogamicin reduces relapse risk in FLT3/ITD acute myeloid leukemia: A report from the children's oncology group

Katherine Tarlock, Todd A. Alonzo, Robert B. Gerbing, Susana C. Raimondi, Betsy A. Hirsch, Lillian Sung, Jessica A. Pollard, Richard Aplenc, Michael R. Loken, Alan S. Gamis, Soheil Meshinchi

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52 Scopus citations

Abstract

Purpose: Gemtuzumab ozogamicin (GO), a calicheamicinconjugated 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 FLT3/ITD. Experimental Design: We analyzed children with FLT3/ITD- positive AML (n = 183) treated on two consecutive Children's Oncology GroupAMLtrials (NCT00070174 and NCT00372593). Outcomes were assessed for FLT3/ITD patients receiving standard chemotherapy with or withoutGO(GO vs. No-GO, respectively), and the impact of consolidation HCT for high-risk FLT3/ITD patients [high FLT3/ITD allelic ratio (ITD-AR)]. Results: For all FLT3/ITD patients, complete remission (CR) rates for the GO versus No-GO cohorts were identical (64% vs. 64%; P = 0.98). Relapse rate (RR) after initial CR was 37% for GO recipients versus 59% for No-GO recipients (P = 0.02), disease-free survival (DFS) was similar (47% vs. 41%; P = 0.45), with higher treatment-related mortality (TRM) in GO recipients (16% vs. 0%; P = 0.008). Among high-risk FLT3/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%; P = 0.007), with a corresponding DFS of 65% versus 40% (P = 0.08), and higher TRM (19% vs. 7%; P = 0.08). Conclusions: CD33 targeting with HCT consolidation may be an important therapeutic strategy in high-risk FLT3/ITD AML and its efficacy and associated toxicity warrant further investigation.

Original languageEnglish (US)
Pages (from-to)1951-1957
Number of pages7
JournalClinical Cancer Research
Volume22
Issue number8
DOIs
StatePublished - Apr 15 2016

Bibliographical note

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© 2015 AACR.

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